ORCID Profile
0000-0002-7130-3530
Current Organisation
University of Adelaide
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Publisher: AMPCo
Date: 08-1997
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1995
DOI: 10.1097/00005344-199506000-00018
Abstract: The effects of inhibiting nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA) on renal vasoconstrictor responses to intrarenally administered norepinephrine (NE) and endothelin-1 (ET-1) were studied in conscious dogs. NE was infused into the renal artery at 0.02, 0.05, 0.1, and 0.2 micrograms/kg/min (15 min at each rate), with the dogs (n = 5) pretreated with either L-NNA 10 mg/kg intravenously (i.v.) or vehicle (250 mM NaHCO3 solution at 2 ml/kg i.v.) NE produced dose-related decreases in renal blood flow (RBF) and renal vascular conductance that were significantly greater after L-NNA pretreatment than after vehicle. ET-1 was infused intrarenally at 2.7 ng/kg/min for 45 min with the dogs (n = 5) pretreated with either L-NNA 10 mg/kg i.v. or vehicle. ET-1 caused a progressive decrease in RBF and renal vascular conductance. In contrast to the results with NE, RBF and renal vascular conductance decreased significantly less in response to ET when the dogs were pretreated with L-NNA as compared with pretreatment with vehicle. Therefore, blockade of NO synthase augmented NE-induced but not ET-induced renal vasoconstriction. The results therefore suggest that NO may act to lessen the renal vascular effects of NE, but this effect does not appear to be generalised to all vasoconstrictors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1976
Publisher: Wiley
Date: 06-1997
DOI: 10.1111/J.1440-1681.1997.TB01219.X
Abstract: 1. To determine whether chronic angiotensin II (AngII) infusion into the renal artery, at a dose which increases systemic arterial pressure, reduces glomerular filtration rate (GFR) and renal blood flow, AngII was infused at 0.5 ng/kg per min into the renal artery or intravenously in chronically instrumented dogs for 1 month. 2. Mean arterial pressure (MAP) rose significantly (P < 0.05) during the infusion of AngII into the renal artery (+7 +/- 2 mmHg on days 26-30). There were no significant changes in GFR or renal blood flow. When the same dose of AngII was infused intravenously, MAP did not change significantly (-2 +/- 2 mmHg) and there were no significant changes in GFR or in renal blood flow. 3. We conclude that AngII infused into the renal artery for 1 month, at a dose which was initially subpressor, causes a rise in arterial pressure that is not associated with impairment of renal function.
Publisher: Wiley
Date: 02-1995
DOI: 10.1111/J.1440-1681.1995.TB01962.X
Abstract: 1. We tested the effects of blockade of nitric oxide synthesis on renal function under conditions of controlled renal artery pressure. Our hypothesis was that endogenous nitric oxides plays a role in the natriuresis that accompanies increased renal perfusion pressure. We used a novel technique which employed an extracorporeal circuit to produce step changes over a wide range of renal artery pressures in pentobarbitone-anaesthetized rabbits. 2. Rabbits were treated with either NG-nitro-L-arginine (NOLA, 20 mg/kg, i.v. n = 8) or its vehicle (n = 8). Renal artery pressure was set (by adjusting the extracorporeal circuit) at 65, 80, 95, 110 and then 130 mmHg respectively, at the beginning of each of five 30 min experimental periods. 3. NOLA treatment caused profound renal vasoconstriction that was largely independent of the level of renal artery pressure, renal blood flow being 35-43% lower in NOLA-treated than in vehicle-treated rabbits across the range of renal artery pressures tested (P = 0.002). NOLA treatment increased filtration fraction (P = 0.02), and tended to reduce glomerular filtration rate (P = 0.09). 4. NOLA-treatment affected sodium excretion in a manner dependent on the legel of renal artery pressure, with the slope of the relationship between sodium excretion and renal artery pressure being lower in NOLA-treated than in vehicle-treated rabbits (P = 0.006). 5. These data provide direct evidence that in anaesthetized rabbits endogenous nitric oxide (i) tonically dilates the renal vasculature across a wide range of renal perfusion pressures, and (ii) enhances sodium excretion to a progressively greater degree as renal artery pressure is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 04-1976
DOI: 10.1038/ICB.1976.17
Abstract: The contributions of the sympathetic nervous system and the adrenal medullary catecholamines to the response of dog hind limb resistance vessels to haemorrhage were examined. Anaesthetized dogs were bled either 30% or 45% of blood volume. There was little difference between the vascular conductance response in untreated hind limbs and sympathectomized limbs. Conductance in limbs that had been both sympathectomized and alpha-adrenergically blocked with phenoxybenzamine was markedly above that of untreated limbs. Blood flow in both the untreated limbs and the sympathectomized limbs was closely similar to that predicted from the pressure-flow curve for the hind limbs obtained in non-bled dogs. Flow was higher than predicted in the limbs with combined sympathectomy and alpha-adrenergic blockade. It is concluded that the sympathetic nervous system exerted little vasoconstrictive influence after haemorrhage, but that circulatory catecholamines exerted a strong vasoconstrictive influence that was opposed in the normal limbs by an almost equally powerful vasodilatory force of undetermined origin.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2003
DOI: 10.1161/01.HYP.0000050961.70182.56
Abstract: The loss of one allele for glial cell line–derived neurotrophic factor (GDNF) results in ≈30% fewer but normal sized glomeruli in young mice. Low nephron number, inherited or acquired, has been linked to increased risk of development of hypertension and renal failure. This study examines whether GDNF heterozygous mice, with an inherent reduction in nephron number, demonstrate a deterioration in renal structure and function and rise in arterial pressure in later life. Fourteen-month-old male GDNF heterozygous (n=7) and wild-type (n=6) mice were anesthetized and prepared for measurement of mean arterial pressure, glomerular filtration rate (GFR), and renal blood flow. After measurement of renal function, kidneys were fixed for stereological determination of total glomerular number and mean glomerular volume. Mean arterial pressure was, on average, 18 mm Hg higher in GDNF heterozygous (98±4 mm Hg) than wild-type mice (80±2 mm Hg P .01). However, GFR (0.656±0.054 versus 0.688±0.076 mL/min per g kidney wt) and renal blood flow (5.29±0.42 versus 4.70±0.34 mL/min per g kidney wt) were not different between groups. Fourteen-month-old GDNF heterozygous mice had ≈30% fewer glomeruli than wild-type mice (9206±934 versus 13440±1275 P .01) and significantly larger glomeruli (4.51±0.39 versus 3.72±0.63×10 −4 mm 3 P .01). Thus, aged GDNF heterozygous mice maintained a normal GFR and renal blood flow despite reduced nephron numbers. The elevated arterial pressure, glomerular hypertrophy, and hyperfiltration demonstrated in the GDNF heterozygous mice at this age may indicate a compensatory mechanism whereby GFR is maintained in the presence of a reduced nephron endowment.
Publisher: Springer Science and Business Media LLC
Date: 10-2001
DOI: 10.1007/BF02332977
Publisher: Wiley
Date: 06-1985
DOI: 10.1111/J.1440-1681.1985.TB02650.X
Abstract: The acute responses to renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. Stenosis of one renal artery produced a rise in arterial pressure and a fall in total peripheral conductance, but no change in cardiac output. The resistance to blood flow of the stenotic kidney 1 h after stenosis was 25% greater than before stenosis. This rise in resistance was due to the resistance of the renal artery stenosis itself. Blood flow to the contralateral kidney fell by 13% (s.e.m. = 3) at 1 h and resistance rose by 39% (s.e.m. = 5). Plasma renin activity was elevated approximately 10 fold. Calculations of changes in peripheral conductances following stenosis showed that the stenotic kidney was responsible for 14% of the fall in total peripheral conductance at 1 h, and the contralateral kidney for 18%. Thus acute renal artery stenosis produced a prompt rise in arterial pressure due to reduced peripheral conductance, of which the two kidneys (stenotic and contralateral) were responsible for one-third.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2003
DOI: 10.1097/00004872-200307000-00031
Abstract: To determine whether 'slow pressor' hypertension from systemic angiotensin (Ang II) infusion was associated with renal vascular structural remodeling of the renal resistance vessels and glomerulus. Ang II (4.5-10 ng/kg per min) or vehicle was infused for 10 days. Renal resistance vascular lumen changes were assessed at 10 days as changes in renal pressure flow and pressure-glomerular filtration rate (GFR) and pressure-Na+ excretion in maximally dilated, isotonically perfused kidneys. Low-dose, initially subpressor Ang II infusion for 10 days increased conscious arterial pressure by 27 mmHg compared to vehicle-infused rats (140 +/- 7 and 113 +/- 2 mmHg, respectively). There was no change in the pressure-flow relationship but the slope of the pressure-GFR relationship was reduced in the rats treated with Ang II. These changes are consistent with equal and opposite pre-and post-glomerular effects (i.e., increased pre-glomerular vessel resistance and reduced post-glomerular vessel resistance) and reduced glomerular ultrafiltration coefficient. There was also a significant reduction in pressure-dependent Na+ excretion. Slow pressor Ang II-induced hypertension was associated with apparent pro-hypertensive changes in the kidney involving pre ost-glomerular vessel remodeling as indicated by an apparent reduction in pre-glomerular lumen dimensions, a reduced glomerular filtration capacity and a reduction in the pressure natriuresis relationship.
Publisher: S. Karger AG
Date: 2000
DOI: 10.1159/000025985
Abstract: To determine how endothelins affect regional kidney blood flow and responses to increased renal artery pressure (RAP), an extracorporeal circuit was established to control RAP independent of the mean systemic arterial pressure (MAP). RAP was first set at ∼65 mm Hg, and endothelin-1 (1 ng/kg/min for 30 min then 0.4 ng/kg/min) or vehicle was infused into the renal artery, or the ET sub A /sub /ET sub B /sub antagonist TAK-044 (3 mg/kg plus 3 mg/kg/h) or vehicle was administered intravenously. RAP was then progressively increased in steps from ∼65 to ∼160 mm Hg. When RAP was ∼65 mm Hg, endothelin-1 increased renal vascular resistance (RVR, 72%), and reduced cortical (CBF, 26%) but not medullary blood flow (MBF). TAK-044 reduced MAP (12%) and RVR (15%) and increased CBF (21%) but not MBF. When RAP was increased, renal blood flow (RBF), glomerular filtration rate, and urine and sodium excretion increased, while MAP fell. These responses were unaffected by endothelin-1. TAK-044 potentiated the increases in RBF and reductions in MAP in response to increased RAP, but did not affect urine and sodium excretion. Plasma renin activity was reduced by endothelin-1 and increased by TAK-044. Thus, both exogenous and endogenous endothelins reduce CBF but not MBF, and reduce plasma renin activity, but neither affect pressure natriuresis.
Publisher: Wiley
Date: 15-02-1994
DOI: 10.1113/JPHYSIOL.1994.SP020057
Abstract: 1. The renal effects of inhibiting nitric oxide (NO) formation using N-nitro-L-arginine (NOLA, 20 mg kg-1) were examined using micropuncture techniques in pentobarbitone-anaesthetized rabbits. 2. Renal vascular resistance doubled from 2.7 +/- 0.5 to 5.0 +/- 1.1 mmHg ml-1 min-1 after NOLA (P < 0.01), with similar percentage increases in both pre- (149 +/- 38%, P < 0.01) and postglomerular (158 +/- 42%, P < 0.01) resistance. 3. Glomerular capillary pressure rose from 33 +/- 1 to 40 +/- 1 mmHg after NOLA (P < 0.01) but despite this, glomerular filtration rate (GFR) and single nephron glomerular filtration rate did not significantly change. 4. Blood pressure increased 18 +/- 1 mmHg (P < 0.001) within 10 min of NOLA administration and remained near this level for the next 90 min. 5. The glomerular ultrafiltration coefficient (Kf) decreased significantly from 0.085 +/- 0.022 to 0.035 +/- 0.006 nl s-1 mmHg-1 (P < 0.05). 6. Urine flow and sodium excretion increased markedly (26 +/- 9 to 337 +/- 102 microliters min-1 and 5 +/- 2 to 342 +/- 12 mumol min-1 respectively, (P < 0.001)) and sodium fractional excretion rose from 1.0 +/- 0.3 to 8.0 +/- 2.2% (P < 0.01). 7. Thus, administration of NOLA to rabbits caused vasoconstriction of both pre- and postglomerular vessels, diuresis and natriuresis without significant change in GFR, and a reduction in Kf. The results suggest that NO may play an important role in the regulation of renal haemodynamics and glomerular function.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1990
Abstract: The renal and systemic changes after stenosis of the left renal artery (n = 5) or sham stenosis (n = 6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component. Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance.
Publisher: American Physiological Society
Date: 11-1985
DOI: 10.1152/AJPHEART.1985.249.5.H956
Abstract: The acute effects of unilateral renal arterial stenosis on systemic and renal hemodynamics were studied in chronically instrumented, conscious dogs. Graded stenosis of one renal artery for 90 min produced graded increases in arterial blood pressure and plasma renin activity and falls in contralateral renal blood flow and total peripheral conductance. There were no significant changes in cardiac output. The changes were transient after mild or moderate renal arterial stenosis but were sustained after severe stenosis. Pentolinium treatment did not significantly affect the hypertension or contralateral renal vasoconstriction caused by moderate or severe renal arterial stenosis. This indicates that the autonomic nervous system did not play a major role in the response to stenosis. In contrast, teprotide abolished the increases in arterial pressure, the contralateral renal vasoconstriction, and the fall in total peripheral conductance in response to stenosis. Thus the acute hypertension following unilateral renal arterial stenosis was due to a decrease in total peripheral conductance caused by decreased conductance of the stenotic kidney due to the stenosis itself (about 20%) vasoconstriction of the contralateral kidney (about 20%), and vasoconstriction of other systemic vasculature (about 60%). The results suggest that angiotensin II was responsible for the vasoconstriction of both the contralateral kidney and the other systemic vasculature.
Publisher: Wiley
Date: 09-1996
DOI: 10.1111/J.1440-1681.1996.TB01179.X
Abstract: 1. Recent physiological experiments have established that increasing the perfusion pressure of the kidney causes the release of vasodepressor substance from the renal medulla. 2. The substance is not a platelet activating factor, a prostaglandin or nitric oxide and the vasodepressor response to increased renal perfusion is not due simply to inhibition of renin release. 3. The mechanisms by which the renomedullary vasodepressor substance lowers arterial pressure remain to be determined. Sympathoinhibition may account for part of the response, but the hypotension still occurs in autonomic ganglion blocked animals. 4. The source of substance appears to be the renomedullary interstitial cells, though the control of the production and release of the substance remain to be determined. 5. The substance may be a lipid but it is yet to be fully isolated and identified. 6. The threshold for release of the substance appears to be close to normal resting arterial blood pressure. 7. Despite strong evidence that the renal medulla releases a vasodepressor hormone in response to increased renal perfusion pressure, much is still to be determined regarding the physiology of this hormone and its involvement in the aetiology of hypertension.
Publisher: American Physiological Society
Date: 04-2002
DOI: 10.1152/AJPREGU.00187.2001
Abstract: ANG II is capable of stimulating expression of immediate early genes such as egr-1 and c- fos in a variety of cultured cells, including cells of renal origin. To investigate whether ANG II can stimulate early growth response gene expression in vivo, we studied the effects of acute renal artery infusion of low-dose ANG II (2.5 ng · kg −1 · min −1 ) or vehicle on the renal expression of c- fos and egr-1 genes in rats. ANG II infusion for 30 or 240 min decreased renal vascular conductance by ∼13 and 8%, respectively, compared with the vehicle group. Expression of the early growth response genes c-fosand egr-1 was analyzed using Northern blot hybridization. No significant upregulation of c- fos or egr-1 mRNA levels was detected in rats that received ANG II for either 30 or 240 min, compared with the vehicle groups. We conclude that ANG II, at doses that cause significant physiological effects, does not increase the renal expression of c- fos or egr-1 genes over periods of up to 4 h in vivo.
Publisher: AMPCo
Date: 02-2015
DOI: 10.5694/MJA14.01475
Publisher: Bentham Science Publishers Ltd.
Date: 03-2005
Publisher: American Physiological Society
Date: 07-1980
DOI: 10.1152/AJPHEART.1980.239.1.H81
Abstract: The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension was investigated in the conscious dog. Intravenous infusion of synthetic arginine vasopressin to elevate plasma levels approximately fivefold to 31 pg/ml caused bradycardia in normal dogs, together with suppression of plasma renin activity and angiotensin II. This plasma level of vasopressin also caused elevation of mean arterial blood pressure in dogs with pharmacological total autonomic blockade. A similar degree of elevation of plasma vasopressin concentration was observed following mild nonhypotensive hemorrhage more severe hemorrhage resulted in an approximate 100-fold increase in plasma vasopressin levels. Severe renal artery constriction in unilaterally nephrectomized dogs caused a marked rise in mean arterial blood pressure, but only a doubling of plasma vasopressin concentration. A suppressor infusion of vasopressin did not potentiate the pressor response to infused angiotensin II. It is concluded that vasopressin may play a role in normal cardiovascular homeostatic responses, but it is unlikely to have a significant direct vasoconstrictor role in the pathogenesis of this form of experimental renal hypertension.
Publisher: Wiley
Date: 12-1995
DOI: 10.1111/J.1440-1681.1995.TB02329.X
Abstract: 1. Increasing renal perfusion pressure, using an extracorporeal circuit in rabbits and dogs, causes release from the kidney of a vasodepressor substance. 2. The hypotensive response occurs in denervated kidneys, and it is not due to platelet activating factor, nitric oxide, prostanoids or suppression of renin release. 3. In the rabbit, the pressure threshold for release of the hypotensive substance appears to be slightly above normal resting pressures. 4. The source of the hypotensive substance is medullary, since the hypotensive response to increased renal perfusion pressure is abolished in dogs and rabbits whose medullae are damaged by bromoethylamine treatment. 5. The chemical nature of the hypotensive substance remains unknown. 6. Thus the renal medulla appears to possess a hypotensive hormone, released in response to elevation of renal perfusion pressure. Many aspects of the physiology and pathology of the substance and its significance in blood pressure regulation remain to be determined.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1988
DOI: 10.1097/00004872-198809000-00005
Abstract: The contribution of renal vascular conductance to the fall in total peripheral conductance during the development of renal wrap hypertension was determined in conscious rabbits. Measurements were made 28 days after renal wrap (n = 9) or sham operation (n = 8). Blood pressure was about 50 mmHg higher in the wrapped group as compared to the sham-operated group. This was due to a fall in total peripheral conductance of about 42%. Cardiac output was not significantly different between wrap and sham groups. Renal vascular conductance was 0.42 ml/min per mmHg lower in the wrap compared to the sham-operated group (P less than 0.001). Total peripheral conductance was 3.93 ml/min per mmHg lower in the wrap compared to the sham group (P less than 0.01). The reduction in renal vascular conductance in wrapped rabbits, which is probably due to compression caused by the thickening renal capsule, accounts for about 10% of the fall in total peripheral conductance. We suggest that this mechanically induced reduction in renal conductance is involved in the initiation and maintenance of the hypertension, but is only a minor contributor to the overall change in blood pressure.
Publisher: Wiley
Date: 02-1984
DOI: 10.1111/J.1440-1681.1984.TB00241.X
Abstract: The responses to 20% haemorrhage were examined in conscious rabbits with or without inhibition of prostaglandin production by indomethacin (5 mg/kg + 0.5 mg/kg per h i.v.). In rabbits not pretreated with indomethacin, haemorrhage lowered mean arterial pressure by 6.3 (s.e.m. = 1.6) mmHg, renal blood flow by 22.8 (s.e.m. = 3.4) ml/min and glomerular filtration rate (GFR) by 3.4 (s.e.m. = 0.6) ml/min, and raised plasma renin activity by 5.2 (s.e.m. = 1.0) ng/ml per h. Pretreatment of the rabbits with indomethacin did not significantly alter the responses to haemorrhage. Mean arterial pressure fell by 10.9 (s.e.m. = 1.8) mmHg, renal blood flow by 24.9 (s.e.m. = 3.9) ml/min and GFR by 4.2 (s.e.m. = 1.8) ml/min and plasma renin activity rose by 3.2 (s.e.m. = 0.5) ng/ml per h. In a separate group of 5 rabbits, angiotensin II was infused at 10, 25 and 50 ng/kg per min i.v. or methoxamine was infused at 10 and 25 micrograms/kg per min i.v. After indomethacin pretreatment, angiotensin II caused a significantly greater rise in mean arterial pressure and greater fall in renal vascular conductance, but there was no effect on the GFR response. In contrast, methoxamine caused significantly smaller falls in GFR, renal blood flow and renal vascular conductance after indomethacin pretreatment. Indomethacin significantly lowered resting GFR but not renal blood flow or arterial pressure. Thus, indomethacin pretreatment accentuated the renal vasoconstriction to angiotensin II, reduced the renal vasoconstriction to methoxamine and had no effect on the responses to haemorrhage. The results therefore suggest that prostaglandins do not act to lessen the renal effects of all vasoconstrictor stimuli, but that the prostaglandin response depends on the nature of the ischaemic stimulus.
Publisher: Wiley
Date: 02-1991
Publisher: Springer Berlin Heidelberg
Date: 1973
Publisher: AMPCo
Date: 2010
Publisher: Wiley
Date: 08-1998
DOI: 10.1111/J.1440-1681.1998.TB02267.X
Abstract: 1. We tested whether chronic intrarenal angiotensin II (AngH) infusion altered renal vascular responsiveness to vasoactive agents, which would provide evidence of vascular structural changes. 2. The renal blood flow (RBF) responses to renal arterial administration of bolus doses of acetylcholine, glyceryl trinitrate, AngH and noradrenaline were measured before commencement of and 1 day after cessation of 28 days intrarenal Angll infusion (0.5 ng/kg per min) in chronically instrumented conscious dogs. 3. The RBF responses to these vasoactive agents were unaltered by chronic intrarenal Angll infusion in conscious dogs. 4. These functional studies provide no evidence for renal vascular hypertrophy in response to chronic intrarenal Angll infusion in conscious dogs.
Publisher: AMPCo
Date: 03-2006
DOI: 10.5694/J.1326-5377.2006.TB00232.X
Abstract: All stakeholders should contribute to enhancing Australia's guidelines for ethical research.
Publisher: Elsevier BV
Date: 02-2004
Publisher: Wiley
Date: 21-06-2006
DOI: 10.1111/J.1440-1681.2006.04391.X
Abstract: 1. High blood flow to the kidney facilitates a high glomerular filtration rate, but total renal O2 delivery greatly exceeds renal metabolic requirements. However, tissue Po2 in much of the renal cortex is lower than may be expected, being similar to that of other organs in which perfusion is closely matched to metabolic demand. 2. The lower than expected renal cortical Po2 is now attributed largely to diffusional shunting of as much as 50% of inflowing O2 from blood within preglomerular arterial vessels to post-glomerular venous vessels. However, the functional significance of this O2 shunting remains unclear. Indeed, this mechanism may appear maladaptive, given the kidney's susceptibility to hypoxic insults. 3. We hypothesize that renal preglomerular arterial-venous O2 shunting acts to protect the kidney from the potentially damaging consequences of tissue hyperoxia. The diffusion of O2 from arteries to veins within the kidney acts to reduce the O2 content of the blood before it is distributed to the renal microcirculation. Because high tissue Po2 may increase the production of reactive oxygen species, we suggest that renal arterial-venous O2 shunting may provide a physiological benefit to the organism by limiting O2 delivery to renal tissue, thereby reducing the risk of cellular oxidation.
Publisher: Elsevier BV
Date: 02-2011
Publisher: American Physiological Society
Date: 12-1997
DOI: 10.1152/AJPREGU.1997.273.6.R1980
Abstract: Chronic intrarenal infusion of angiotensin II (0.5 ng ⋅ kg −1 ⋅ min −1 ) in dogs increases arterial pressure. In the present study we determined whether this was associated with changes in cardiac output or in total peripheral resistance. Mean arterial pressure did not change initially but was significantly increased over days 14- 28 of the infusion period (+6 ± 2 mmHg), as was total peripheral resistance (+4 ± 2 mmHg ⋅ min ⋅ l −1 ). Neither cardiac output, renal blood flow, nor glomerular filtration rate was significantly changed over this period. To determine the influence of the autonomic nervous system on the developing hypertension, periodic acute autonomic ganglion blockade was performed. Before angiotensin II infusion ganglion blockade reduced total peripheral resistance and increased cardiac output, and this effect was similar across the 4 wk of angiotensin II infusion. Systemic hemodynamics were not affected by intravenous angiotensin II infusion (0.5 ng ⋅ kg −1 ⋅ min −1 ). Thus intrarenal infusion of low-dose angiotensin II produced a chronic increase in arterial pressure due to an action within the kidney. The hypertension was associated with increased total peripheral resistance but not with marked changes in cardiac output or renal function or in the influence of the autonomic nervous system on systemic hemodynamics.
Publisher: AMPCo
Date: 06-1998
Publisher: American Physiological Society
Date: 02-1994
Publisher: Wiley
Date: 08-1989
DOI: 10.1111/J.1440-1681.1989.TB01621.X
Abstract: 1. Renal cellophane wrapping to produce hypertension causes thickening of the capsule of the kidney. To determine whether this compresses the kidney, deep renal vein wedge pressure was measured as an estimate of tissue pressure in anaesthetized rabbits 1 month after cellophane wrapping (n = 5) or a sham operation (n = 3). 2. Renal vein wedge pressure was 18.3 +/- 2.0 mmHg in hypertensive rabbits and 8.4 +/- 1.1 mmHg in the sham-operated rabbits. 3. Arterial pressure was raised or lowered with angiotensin II or glyceryl trinitrate, respectively. Arterial and wedge pressures were approximately linearly related and, at any given arterial pressure, wedge pressure was approximately 8 mmHg higher in the cellophane-wrapped kidney than in the kidney of the sham-operated group. 4. These results, showing that renal wedge pressure is elevated in renal wrap rabbits, indicate that the kidneys are compressed, probably by the thickened renal capsule. This may explain the increased renal vascular resistance seen in this form of hypertension.
Publisher: Springer Science and Business Media LLC
Date: 07-2011
DOI: 10.1038/475027A
Publisher: Springer Science and Business Media LLC
Date: 10-1991
DOI: 10.1007/BF00371101
Abstract: Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The differences in inflammatory cells and the factors contributing to these differences were examined in the airways of patients with COPD who do not currently smoke. Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (FEV(1)) 59 (13)% predicted and 11 non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV(1) 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. Patients with COPD had more mucosal EG2+ cells (eosinophils) (median (range) 40 (0-190) versus 5 (0-40) cells/mm(2), p = 0.049) and CD68+ cells (1115 (330-2920) versus 590 (450-1580) cells/mm(2), p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29-94) versus 36 (18-60)%, p = 0.001) and eosinophils (1.2 (0-8.5) versus 0.2 (0-3.1)%, p = 0.008), BAL fluid eosinophils (0.4 (0-1.7) versus 0.2 (0-0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115-23 760) versus 121 (35-218) ng/ml, p<0.001). Concentrations of ECP expressed per eosinophil were not higher. Patients with COPD with high mucosal EG2+ cell numbers also had high mucosal CD4+ cell numbers. Sputum eosinophilia was associated with a decrease in FEV(1)/VC and BAL fluid eosinophilia with a decrease in mucosal NP57+ cells (neutrophils). Subjects with COPD who do not currently smoke have increased numbers of inflammatory cells. Eosinophils are increased in number in the airways in COPD but do not seem to be activated. The increased eosinophil numbers are probably due to recruitment as a result of ongoing inflammation. Macrophages and lymphocytes may play a part in this inflammation.
Publisher: Wiley
Date: 05-1991
Publisher: Portland Press Ltd.
Date: 1978
DOI: 10.1042/CS055251S
Abstract: 1. The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension in the conscious dog was investigated. 2. Infusion of synthetic arginine vasopressin to elevate plasma levels approximately five-fold caused bradycardia in normal dogs and increase in mean arterial blood pressure in dogs with pharmacological autonomic blockade. 3. A similar degree of elevation of plasma vasopressin concentration was observed after mild non-hypotensive haemorrhage. 4. Renal artery constriction in unilaterally-nephrectomized dogs caused a rise in plasma renin activity and only a doubling of plasma vasopressin concentration, but a marked rise in mean arterial blood pressure. 5. Vasopressin may play a role in normal cardiovascular homeostatic responses, but its role in the pathogenesis of this form of hypertension is unlikely to be significant.
Publisher: Canadian Science Publishing
Date: 08-1987
DOI: 10.1139/Y87-245
Abstract: In renal artery stenosis severe enough to cause hypertension, angiotensin II maintains glomerular filtration rate (GFR) both in the initial high renin phase of hypertension and later when plasma levels are normal. Angiotensin II also maintains GFR in less severe stenosis, which does not cause hypertension. This homeostatic action of angiotensin II to maintain GFR has minimal effects on blood flow. In renal-wrap hypertension, plasma renin levels are elevated for longer than after renal artery stenosis, but in other respects this initial phase of the hypertension is similar to that after renal artery stenosis. GFR is reduced, the rate of development of hypertension is accelerated by angiotensin II, and angiotensin II maintains the glomerular filtration fraction. Renal resistance is markedly increased owing to both compression of the kidney by the hypertrophying renal capsule and to angiotensin II. Thus angiotensin II apparently plays a primarily homeostatic role in renovascular hypertension to maintain glomerular ultrafiltration. It is suggested that the angiotensin II may be formed intrarenally and may act on sites other than resistance blood vessels.
Publisher: Wiley
Date: 05-1995
DOI: 10.1111/J.1440-1681.1995.TB02013.X
Abstract: 1. The involvement of nitric oxide (NO) and platelet activating factor (PAF) in the systemic depressor responses to increased renal perfusion pressure (RPP) were investigated. 2. In anaesthetized rabbits, the left kidney was perfused via an extracorporeal circuit which allowed RPP to be increased from 65 mmHg to 125 mmHg. The response of systemic blood pressure (SBP) to increasing RPP was measured in the same rabbits. 3. One group of rabbits (n = 5) was treated with NG-nitro-L-arginine (NOLA) to inhibit NO synthase activity (20 mg/kg i.v. bolus). Another group (n = 5), received 250 mmol/L NaHCO3 (4 mL/kg bolus) as vehicle treatment. 4. Following an increase in RPP to 125 mmHg, SBP fell at a rate of 0.43 +/- 0.06 mmHg/min in the vehicle treated rabbits. After NO synthase inhibition the rate of fall in SBP of 0.34 +/- 0.07 mmHg/min was not significantly different from that in the vehicle group (P = 0.3). 5. Blockade of NO synthesis did not alter the renal blood flow, renal vascular resistance changes and pressure-related natriuresis and diuresis responses to increased RPP to 125 mmHg. 6. PAF receptor blockade, using WEB 2086 (0.5 mg/kg plus 0.5 mg/kg/h), did not alter the systemic, renal haemodynamic or urinary responses to increasing renal perfusion pressure to 125 mmHg. 7. These findings indicate that neither NO nor PAF play an important role in the blood pressure lowering activity, intrarenal haemodynamics and urinary excretory responses observed when RPP was increased to a level within the physiological range.
Publisher: Springer US
Date: 2007
DOI: 10.1007/978-0-387-71764-7_13
Abstract: Recently, a combined probe has been developed capable of simultaneous measurement of local tissue pO2 (fluorescence oximetry) and microvascular perfusion (laser Doppler flux) within the same local region. The aim of the current study was to test the utility of these combined probes to measure pO2 and perfusion in the kidney. Studies were performed in anesthetized, artificially ventilated rabbits (n=7). Baseline measurements of renal medullary perfusion and pO2 obtained using combined probes (537 +/- 110 units & 28.7 +/- 6.l mmHg, respectively) were indistinguishable from those obtained using independent probes (435 +/- 102 units & 26.9 +/- 6.4 mmHg). Baseline measurements of renal cortical pO2 were also similar between combined (9.7 +/- 1.6 mmHg) and independent probes (9.5 +/- 2.3 mmHg). Baseline levels of cortical perfusion however, were significantly greater when measured using independent probes (1130 +/- 114 units) compared to combined probes (622 +/- 59 units P < 0.02). Relative changes in perfusion and pO2 resulting from graded stimulation of the renal nerves were not significantly different when measured using combined probes to those obtained using independent probes. We conclude that combined probes are equally suitable to independent probes for tissue pO2 and microvascular perfusion measurement in the kidney. Our results raise some concerns regarding the accuracy of these OxyLite fluorescence probes for pO2 measurement in the kidney, particularly within the renal cortex.
Publisher: Wiley
Date: 09-1978
DOI: 10.1111/J.1440-1681.1978.TB00706.X
Abstract: 1. The renal artery of conscious dogs was acutely narrowed over 30 s to reduce renal artery pressure distal to the stenosis to 40 mmHg and the stenosis was maintained for 1 h. The distal renal artery pressure was rapidly restored to a plateau slightly below pre-stenosis values within 10--15 min. Rises in systemic blood pressure and plasma renin activity were small and transient. 2. This restoration was an active process, mediated by the intrarenal effects of angiotensin II (AII), since it was greatly diminished or abolished when the renal artery was narrowed in the presence of angiotensin I-converting enzyme inhibitor or angiotensin receptor antagonist (1-Sar-8-Ile AII). However, it was not diminished by 'total' autonomic effector blockade. 3. This angiotensin II-mediated restoration of renal artery pressure may be of homeostatic significance for the maintenance of glomerular filtration rate.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1988
Abstract: The oral mucosa is relatively resistant to human immunodeficiency virus type 1 (HIV-1) transmission. The mechanisms contributing to this resistance remain incompletely understood, but may include HIV-induced synthesis of innate immune factors. We used fully differentiated oral epithelium as a surrogate for the oral mucosa in vivo, exposed it to X4- and R5-tropic HIV-1 in culture, and quantified mRNA expression of six innate immune factors. Neither virus increased expression of human beta defensin 2 (hBD-2) mRNA over supernatants from uninfected lymphoblast controls. HIV-1 also failed to induce mRNA of four additional innate immunity-related genes. Similar results were obtained with oral monolayer epithelial cells. Interestingly, the X4-tropic virus inhibited mRNA expression of hBD-2, and of three of the other factors, at higher dosages in the differentiated oral epithelium but not the monolayers. The failure of HIV-1 to induce innate immune factors in the differentiated epithelium was not due to a lack of tissue penetration, as we detected fluorescence-tagged virions up to 30 mum deep from the apical surface. HIV-1 does not trigger de novo innate immune factor synthesis in oral epithelium, pointing to the role of a constitutive innate immunity for protection against HIV-1 in the oral cavity.
Publisher: Informa UK Limited
Date: 1994
DOI: 10.3109/08037059409101532
Abstract: Bromoethylamine (BEA, 30-40 mg/kg) was administered to dogs to determine whether damage to the inner medulla of the kidney, the putative source of a depressor hormone, causes hypertension in this species. Bromoethylamine produces hypertension in rats but this has not been confirmed in other species, although we have shown that this dose of BEA in dogs abolishes the release of a reno-medullary vasodepressor hormone in response to marked increases in renal perfusion pressure. During acute BEA administration over 1 h to conscious dogs, there were no significant effects on renal blood flow, arterial pressure or total peripheral resistance, but there was a significantly greater diuresis compared to vehicle administration. Over the first 10-14 days after BEA, daily urine output rose 5-10 fold initially and plasma creatinine concentration rose markedly. There was no significant effect on arterial pressure, cardiac output, total peripheral resistance, or renal blood flow over this period. BEA administration caused extensive damage to the thin limbs of the loops of Henle, widespread thrombosis of blood vessels and haemorrhage into the interstitium of the dog renal medulla. Reno-medullary interstitial cells were devoid of lipid droplets, were synthetic, and were associated with increased amounts of extracellular matrix. Thus extensive renal medullary damage by BEA administration to conscious dogs did not alter resting systemic haemodynamics, and these results therefore provide no evidence for a role for the medulla in the maintenance of resting arterial pressure in the dog.
Publisher: Elsevier BV
Date: 09-1975
Abstract: Blood utilization in 400 consecutive adult patients undergoing a wide variety of cardiovascular operations requiring cardiopulmonary bypass was documented following institution of: 1) complete oxygenator hemodilution 2) intraoperative phlebotomy and autologous transfusion 3) infusion of residual oxygenator red cells and 4) use of reconstituted frozen cells in patients whose blood type was uncommon. These techniques have resulted in an average utilization of 4.8 units of blood per adult patient. Fourteen patients required no blood at all and a total of 259 patients required less than 5 units of blood during their entire hospital course. Physiologic effects of this blood program and hemodilution were evaluated in ten patients and the results indicate that marked reduction of red cell mass by hemodilution with hypothermia and low flow perfusion is not detrimental to satisfactory whole blood oxygenation during open heart surgery.
Publisher: Springer Science and Business Media LLC
Date: 10-1991
DOI: 10.1007/BF01191730
Publisher: Springer Science and Business Media LLC
Date: 12-1999
Abstract: We tested whether the opioid antagonist naloxone affects responses to plasma volume expansion (PVE) in conscious rabbits. Under basal conditions, naloxone (6 mg x kg-(1) plus 0.3 mg x kg(-1) x min(-1) i.v.) had no observable effect, except to slightly reduce heart rate. During vehicle treatment, PVE (Haemaccel 1 ml x kg(-1) min(-1) for 30 min plus 0.2 ml x kg(-1) x min(-1) for 60 min i.v.) reduced haematocrit by 7.1+/-0.8% (from 34.8+/-1.1%), and increased central venous pressure by 3.0+/-0.9 mmHg (from -2.8+/-1.5 mmHg), cardiac output by 42+/-9 ml min(-1) x kg(-1) (from 152+/-17 ml x min(-1) x kg(-1)), systemic vascular conductance by 0.49+/-0.11 ml x min(-1) x mmHg(-1) kg(-1) (from 1.58+/-0.23 ml x min(-1) x mmHg(-1) x kg(-1)), urine flow by 0.13+/-0.04 ml x kg(-)x min(-1) (from 0.12+/-0.02 ml kg(-1) x min(-1)) and sodium excretion by 21+/-5 micromol x kg(-1) min(-1) (from 5+/-2 micromol x kg(-1) x min(-1)). During naloxone treatment, the PVE-induced changes in haematocrit and central venous pressure were similar to those during vehicle treatment, but the increases in cardiac output (24+/-7 ml kg(-1) min(-1)), systemic vascular conductance (0.25+/-0.05 ml min(-1) x kg(-1) x mmHg(-1)), urine flow (0.09+/-0.03 ml x kg(-1) min(-1)) and sodium excretion (11+/-4 micromol x kg(-1) x min(-1)) were 31-49% less. These observations indicate that endogenous opioids mediate some of the circulatory and renal excretory responses to PVE in conscious rabbits.
Publisher: Wiley
Date: 06-12-2001
DOI: 10.1046/J.1440-1681.2001.03590.X
Abstract: 1. Angiotensin (Ang) II causes growth-related effects on vascular smooth muscle cells in vitro and in vivo. 2. Chronic infusions of AngII systemically, at doses that are initially subpressor, result in slowly progressive increases in arterial pressure ('slow-pressor' hypertension). It has been suggested that the hypertension is due to induced growth in systemic resistance vessel walls by the AngII infusions. 3. We report the results of several studies investigating whether there are also induced structural changes in renal resistance vessels during chronic AngII infusions. We have developed models in Sprague-Dawley rats in which low-dose AngII infusions, either into the renal artery (thus restricting the effects to the kidney) or systemically, result in hypertension. 5. In both models, we have evidence suggesting that chronic AngII infusions have resulted in apparent structurally induced reductions in renal vasculature lumen upstream to the glomerulus. 6. The role of these renal changes in the development of the hypertension remain to be determined.
Publisher: Informa UK Limited
Date: 1989
DOI: 10.3109/10641968909035291
Abstract: Atrial natriuretic peptide (ANP, 2 micrograms/min) was infused intravenously into rabbits four weeks after renal wrap or sham operation. Mean arterial pressure (MAP) averaged 132 +/- 4 mmHg in the renal wrapped rabbits and 89 +/- 3 mmHg in the sham rabbits, and glomerular filtration rate (GFR) was significantly lower in the hypertensive rabbits (6.2 +/- 1.0 ml/min) than in sham rabbits (8.9 +/- 0.7 ml/min). In sham rabbits, ANP caused a significant diuresis, natriuresis and increase in GFR. Enalapril pretreatment blunted these responses. In the hypertensive rabbits, ANP reduced mean arterial pressure but did not cause significant diuresis or natriuresis or change in GFR. Enalapril pretreatment did not significantly alter this response to ANP. In separate experiments, nitroprusside was infused to lower arterial pressure in hypertensive rabbits by a similar amount to that achieved with ANP and this reduced GFR, sodium and urine excretion rates. Thus ANP maintained GFR and sodium excretion in hypertensive rabbits compared to an equihypotensive dose of nitroprusside. In summary, ANP did not cause natriuresis or diuresis in renal wrapped kidneys at a dose which was effective in normal kidneys, but did maintain GFR, sodium and water excretion rates, compared to an equally hypotensive dose of nitroprusside.
Publisher: AMPCo
Date: 09-2009
DOI: 10.5694/J.1326-5377.2009.TB02778.X
Abstract: To assess whether knowledge of insurance implications influenced uptake of genetic testing by participants in a research study of the causes of colorectal cancer. Analysis of uptake of genetic testing by participants in the population-based Victorian Colorectal Cancer Family Study during two periods: from 1999 to 2003, when participants were not informed of any potential effect of genetic testing conducted during the study on their eligibility for new insurance policies and from 2003 to 2006, when the protocol was changed to provide participants with information on the potential effect of genetic testing on insurance eligibility. Uptake of genetic testing for germline mutations in DNA mismatch repair (MMR) genes at a family cancer clinic. The proportion of participants who declined genetic testing among those informed of insurance implications was more than double the proportion among those without this knowledge (29/59 [49%] v 9/47 [19%] P = 0.002). This difference could not be explained statistically by adjusting for measured putative predictors. Identification of people with a mutation in an MMR gene has clinical importance, and such screening may be a cost-effective way to reduce the burden of colorectal cancer in the community. If people are choosing not to obtain genetic information because of how it will affect their eligibility for insurance, reforms to existing insurance practices are indicated.
Publisher: S. Karger AG
Date: 1986
DOI: 10.1159/000173099
Abstract: Morphological changes in the macula densa have been studied during the infusion of diuretic agents into the renal artery of anesthetized dogs. The kidneys were fixed by rapid high pressure perfusion with glutaraldehyde. Large basolateral intercellular spaces were seen between macula densa cells in control kidneys, but the number and extent of these spaces were strikingly reduced during the natriuresis and diuresis induced by the infusion of frusemide, ethacrynic acid or mannitol. Natriuresis and diuresis produced by the intravenous infusion of large volumes of 0.9% NaCl solution also resulted in closure of these spaces. No simple relationship existed between changes in plasma renin activity and closure of the spaces between macula densa cells during these procedures. A distinctive, membrane-bound, vesicle-containing structure was identified between the basolateral processes of the cells of each macula densa the function of this structure awaits elucidation. We suggest that changes in the size of the basolateral intercellular spaces of the macula densa reflect changes in fluid flux between the distal tubule and the interstitium of the juxtaglomerular apparatus.
Publisher: American Physiological Society
Date: 2003
DOI: 10.1152/AJPREGU.00061.2002
Abstract: We examined the extent of renal medullary blood flow (MBF) autoregulation in pentobarbital-anesthetized rabbits. Two methods for altering renal arterial pressure (RAP) were compared: the conventional method of graded suprarenal aortic occlusion and an extracorporeal circuit that allows RAP to be increased above systemic arterial pressure. Changes in MBF were estimated by laser-Doppler flowmetry, which appears to predominantly reflect erythrocyte velocity, rather than flow, in the kidney. We compared responses using a dual-fiber needle probe held in place by a micromanipulator, with responses from a single-fiber probe anchored to the renal capsule, to test whether RAP-induced changes in kidney volume confound medullary laser-Doppler flux (MLDF) measurements. MLDF responses were similar for both probe types and both methods for altering RAP. MLDF changed little as RAP was altered from 50 to ≥170 mmHg (24 ± 22% change). Within the same RAP range, RBF increased by 296 ± 48%. Urine flow and sodium excretion also increased with increasing RAP. Thus pressure diuresis/natriuresis proceeds in the absence of measurable increases in medullary erythrocyte velocity estimated by laser-Doppler flowmetry. These data do not, however, exclude the possibility that MBF is increased with increasing RAP in this model, because vasa recta recruitment may occur.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1998
Abstract: Abstract —We have previously shown that chronic treatment with angiotensin-converting enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall in spontaneously hypertensive rats (SHR). In this study we determined the effects of perindopril on the functional properties of the renal vasculature in vivo and on its resistance to flow at maximal dilatation in vitro, a measure of vessel lumen diameter. Two groups of SHR were studied: untreated or treated with perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10 weeks, (1) vessel lumen characteristics were assessed using a maximally dilated in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phenylephrine) administered into the renal artery were measured in vivo (anesthetized rats). Mean arterial pressure was significantly lower in conscious SHR treated with perindopril (132±2 versus 97±2 mm Hg, P .001). In vitro, the pressure-flow relationship and the pressure–glomerular filtration rate relationship were both shifted significantly to the left ( P .001). The perindopril-treated kidneys began filtering at a significantly lower threshold perfusion pressure than nontreated controls ( P .001). In vivo, renal vasoconstrictor responses to increasing doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR ( P .05). Thus, chronic ACEI increased average renal vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling of the preglomerular vasculature around a greater lumen.
Publisher: AMPCo
Date: 12-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1994
Abstract: We investigated the relation between renal perfusion pressure and the release of a renal vasodepressor substance in vivo to determine whether this substance was released at physiological pressures. We perfused the left kidneys of anesthetized rabbits using an extracorporeal circuit that allowed renal perfusion pressures to be set at 65 mm Hg (control) and increased to 95, 125, 155, or 185 mm Hg for 30-minute experimental periods. Systemic blood pressure did not change significantly when renal perfusion pressure was maintained at 65 mm Hg throughout. When renal perfusion pressure was increased to 95, 125, 155, or 185 mm Hg, systemic blood pressure fell significantly at rates of 0.17 +/- 0.04, 0.79 +/- 0.31, 0.60 +/- 0.11, and 2.18 +/- 0.79 mm Hg/min, respectively (P .05). Restoration of renal perfusion pressure to 65 mm Hg abruptly reversed the falls in systemic blood pressure in each group. There was a natriuresis and diuresis that were both pressure related and progressive in the face of each constant level of increased renal perfusion pressure. In summary, there was a continuum of arterial vasodepressor responses across a renal perfusion pressure range from resting pressure to 185 mm Hg. We suggest that the threshold level for the release of significant amounts of a renal medullary depressor substance, probably medullipin, is just above normal arterial blood pressure and that the rate of release increases with increasing arterial pressure.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409062567
Abstract: Identical degrees of renal artery stenosis were induced in 5 dogs on two separate occasions once during continuous inhibition of angiotensin I converting enzyme with enalapril, and once with the dogs untreated. Arterial pressure rose about 25 mm Hg during 3 days of stenosis in untreated dogs, due to increased total peripheral resistance. When the dogs were treated with enalapril, blood pressure had risen 14.5 +/- 3.4 mm Hg 24 hours after stenosis due to a 35% increase in cardiac output while total peripheral resistance fell by 16%. By the third day, blood pressure had returned to pre-stenosis levels, cardiac output was close to normal and total peripheral resistance had increased. The stenosis on the renal artery increased the resistance to blood flow of the kidneys in both untreated and enalapril treated dogs. This increase in kidney resistance in the untreated dogs accounted for about 30% of the change in total peripheral resistance. In the enalapril treated dogs, the increased kidney resistance helped offset the vasodilatation in the rest of the vasculature. These results suggest that angiotensin II mediated vasoconstriction of nonrenal vascular beds was responsible for about 2/3 of the hypertension following renal artery stenosis, and the resistance of the stenosis responsible for about 1/3.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044063
Abstract: Adrenaline was infused intravenously into conscious dogs to test whether chronically elevated plasma levels can produce arterial hypertension. Adrenaline infused at 12.5 micrograms/kg/hr from 4 days produced no change in mean arterial pressure (1.1 +/- 2.7 mmHg) despite raising plasma adrenaline concentrations from 49 +/- 20 pg/ml to 1420 +/- 279 pg/ml. Myocardial tissue levels of adrenaline averaged 435 ng/g, compared to 20 ng/g in vehicle infused dogs. Longer infusions of adrenaline (11 days) at doses from 1.25 micrograms/kg/hr to 12.5 micrograms/kg/hr were also without significant effect on arterial blood pressure. In contrast, infusion of noradrenaline at 6.25 micrograms/kg/hr for 11 days produced sustained elevation of mean arterial pressure (11.7 +/- 5.1 mmHg). Although adrenaline infusion alone did not alter arterial pressure, a small rise (5.6 +/- 1.6 mmHg) was measured when the dogs were also given cortisone (50 mg twice daily). These results are therefore not in accord with the hypothesis that increased plasma levels of adrenaline may cause hypertension by activation of pre-junctional beta-adrenoceptors. However simultaneous administration of adrenaline and cortisone did elevate blood pressure, indicating that increases in both adrenal cortical and medullary hormones may be required to produce hypertension.
Publisher: Wiley
Date: 06-1980
DOI: 10.1111/J.1440-1681.1980.TB00075.X
Abstract: 1. Plasma renin and arterial pressure responses to acute renal artery pressure reduction were compared in intact dogs and "autonomically-blocked" dogs subjected to adrenalectomy, chronic guanethidine treatment and acute vagal block (methscopolamine). 2. Following reduction of renal artery pressure plasma renin activity and concentration rose more in the autonomically blocked dogs than in the intact dogs. When renal artery pressure was held at 30 mmHg for 1 h, plasma renin activity rose by 19.1 ng/ml per h (range 11.6-28.7) in autonomically blocked dogs and 3.65 ng/ml per h (range 1.54-5.89) in intact dogs. When renal artery pressure was held at 60 mmHg plasma renin activity rose 3.28 ng/ml per h (range 2.4-4.7) and 1.90 ng/ml per h (range 1.30-3.56), respectively. 3. Arterial blood pressure also rose more in autonomically blocked dogs in accord with the greater rise in plasma renin activity. The relationships between the increases in arterial pressure and plasma renin were closely similar in the two groups. 4. We conclude that the release of renin and increase in arterial blood pressure in response to renal artery stenosis is normally inhibited by arterial baroreflexes.
Publisher: AMPCo
Date: 06-2011
Publisher: AMPCo
Date: 09-1992
Publisher: Wiley
Date: 02-2002
DOI: 10.1113/JPHYSIOL.2001.013280
Abstract: Increasing renal artery pressure (RAP) activates pressure diuresis/natriuresis and inhibits renal renin release. There is also evidence that increasing RAP stimulates release of a putative depressor hormone from the renal medulla, although this hypothesis remains controversial. We examined the relative roles of these antihypertensive mechanisms in the acute depressor responses to increased RAP in anaesthetized rabbits and rats. In rabbits, an extracorporeal circuit was established which allows RAP to be set and controlled without direct effects on systemic haemodynamics. When RAP was maintained at approximately 65 mmHg, cardiac output (CO) and mean arterial pressure (MAP) did not change significantly. In contrast, when RAP was increased to approximately 160 mmHg, CO and MAP fell 20 +/- 5 % and 36 +/- 5 %, respectively, over 30 min. Urine flow also increased more than 28-fold when RAP was increased. When compound sodium lactate was infused intravenously at a rate equal to urine flow, neither CO nor MAP fell significantly in response to increased RAP. In 1 kidney-1 clip hypertensive rats, MAP fell by 54 +/- 10 mmHg over a 2 h period after unclipping. In rats in which isotonic NaCl was administered intravenously at a rate equal to urine flow, MAP did not change significantly after unclipping (-14 +/- 9 mmHg). Our results suggest that the depressor responses to increasing RAP in these experimental models are chiefly attributable to hypovolaemia secondary to pressure diuresis/natruresis. These models therefore appear not to be bioassays for release of a putative renal medullary depressor hormone.
Publisher: Wiley
Date: 10-1980
DOI: 10.1111/J.1440-1681.1980.TB00098.X
Abstract: 1. In rats treated continuously with captopril (80 microgram/h, i.p.), for 2 days, blood pressure decreased and adrenal angiotensin II receptor concentration was decreased from 160 fmol/mg protein (s.e.m. = 9) in controls to 131 fmol/mg protein (s.e.m. 7, P P > 0.05). 2. Vascular reactivity, defined as the pressor response to exogenous angiotensin II, increased concurrently by 166 and 33% respectively. 3. In anaesthetized dogs (n = 8), captopril (1.5 mg/kg, i.v.) caused a fall in blood pressure, and uring bradykinin excretion increased from 1-08 (s.e.m. = 0.14) to 1.64 microgram/h (s.e.m. = 0.33, P < 0.025) at 15 min. Renal blood flow increased significantly (P < 0.01) with no change in glomerular filtration rate, and there was no change in either renal venous or arterial blood bradykinin levels. 4. Thus, converting enzyme inhibition produces transient secondary changes in angiotensin receptors and vascular reactivity. Increased urine bradykinin probably reflects decreased catabolism of intrarenal bradykinin. The hypotensive effect of captopril may be due in part to raised levels of bradykinin in the kidney.
Publisher: Wiley
Date: 03-1983
DOI: 10.1113/JPHYSIOL.1983.SP014570
Abstract: To examine the role of prostaglandins in physiologically induced renin release, we reduced renal artery pressure within the autoregulatory range in chronically instrumented conscious dogs with aspirin, indomethacin or no pre-treatment. In untreated dogs, reduction of renal artery pressure to 60 mmHg for 90 min produced rises in plasma renin activity (+ 5.4 +/- 1.0 ng ml.-1 hr-1) and mean arterial pressure (+ 17 +/- 2 mmHg) without significant effect on renal blood flow (n = 13). Aspirin pre-treatment (2 X 25-40 mg kg-1 orally) had no effect on the renin, arterial pressure or renal blood flow responses to renal artery pressure reduction (n = 7). In contrast, indomethacin pre-treatment (2 X 2-3 mg kg-1 orally) significantly lessened the increase in plasma renin activity during reduced renal artery pressure (+ 2.0 +/- 0.3 ng ml.-1 hr-1, n = 11). The relative effectiveness of aspirin and indomethacin in inhibiting prostaglandin production in the kidney was then tested in separate experiments by measuring the renal blood flow responses to renal artery injections of arachidonate (5-200 micrograms kg-1). In the doses used above, aspirin markedly attenuated the blood flow response to arachidonate but indomethacin had almost no effect. Both aspirin and indomethacin abolished the hypotensive effect of intravenous arachidonate (0.5 mg kg-1). These results tentatively suggest that indomethacin may not effectively inhibit renal prostaglandin production in conscious dogs at the doses used in these experiments. Thus the reduced renin release in response to lowered renal artery pressure in indomethacin pre-treated dogs may have been due to another, non-prostaglandin action of indomethacin. The results from the aspirin pre-treated dogs suggest that prostaglandins are not involved in the release of renin in response to reduced renal artery pressure in conscious dogs.
Publisher: Wiley
Date: 03-1987
DOI: 10.1111/J.1440-1681.1987.TB00388.X
Abstract: 1. Renal artery stenosis was induced in anaesthetized dogs, and the kidney rapidly fixed after 30 min. 2. Electron microscopy revealed marked folding of the paramesangial basement membrane in stenotic kidneys (n = 7). The extent of this folding was significantly less in dogs treated with captopril (n = 6). 3. It is suggested that this folding reflects angiotensin II-induced contraction of the mesangial cells, which may help maintain glomerular filtration rate following stenosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1979
Abstract: Capsulated Haemophilus influenzae type b and two spontaneous mutants (classes I and II variants) were characterized by transmission and scanning electron microscopy. When cells were treated with type b-specific antiserum prior to manipulations for electron microscopy, sectioned capsulated cells had electron-dense, fibrous capsular antigen-antibody complexes around them. In negatively stained preparations, the complexes appeared as electron-transparent zones surrounding cells. In contrast, only residual electron-dense, extracellular material was seen in sectioned, untreated, capsulated cells, and electron-dense "bridges" connected adjacent cells in negatively stained preparations. No extracellular capsular material was seen around the class I and II variants. Characteristic electron-translucent regions were always observed within the cytosol of the class I cells, both in thin sections and by negative staining. These areas were located adjacent to the cell envelope separating the plasma membrane from the dense cytoplasmic matrix. At times, electron-dense, thread-like material extended from the dense cytoplasmic matrix to the plasma membrane. No such regions were seen in the capsulated and class II cells. Class I cells fixed with methanol or suspended in NaCl or phosphate-buffered saline prior to treatment with fluorescein-tagged type b-specific antiserum (FTA reagent) exhibited, by immunofluorescence, patches of capsular antigen along their sides. However, when fixed with glutaraldehyde or OsO4 or suspended in tris-(hydroxymethyl)aminomethane plus Ca2+ buffer prior to treatment with FTA reagent, no patches of capsular antigen were seen. Subsequent exposure of the latter cells to methanol followed by treatment with FTA reagent resulted in the reappearance of the patches of capsular antigen. Thus, in the class I variant the capsular antigen is unlikely to be surface located. Scanning electron microscopy revealed that class I and II variant cells within undisturbed colonies were regularly aligned side-by-side, whereas cells within colonies of the capsulated strain were randomly distributed.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1983
DOI: 10.1097/00004872-198312000-00005
Abstract: Serial measurements of mean arterial pressure and glomerular filtration rate (GFR) were made in rabbits before and 10, 28 and 56 days after bilateral renal cellophane wrap (n = 8) or sham operation (n = 6). No significant changes were seen 10 days after renal wrap, but by 28 days GFR was reduced by 50 +/- 3% and mean arterial pressure had risen by 42 +/- 5 mmHg. No significant further changes occurred over the subsequent month. Changes in plasma renin activity after renal wrapping were not significantly different to those seen after sham operation. In a separate series of experiments, renal extraction ratio of para-aminohippurate (PAH), 28 days after renal wrap, averaged 63 +/- 4% (n = 6) compared to 83 +/- 2% (n = 5) after sham operation. Calculated renal blood flow of the hypertensive rabbits was only about 40% of that in the sham operated rabbits. Thus large reductions in GFR, renal blood flow and PAH extraction ratio occurred following bilateral renal wrapping and these changes may reflect compression of the kidney by the cellophane induced fibrous capsule. These reductions occurred concomitantly with the rise in arterial blood pressure.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1038/543179A
Publisher: Wiley
Date: 09-1981
DOI: 10.1111/J.1440-1681.1981.TB00758.X
Abstract: 1. Administration of captopril (1.5 mg/kg i.v.) to anaesthetized dogs was associated with an increase in renal blood flow of 56 ml min-1 (s.e.m. = 13, n = 9) despite a significant fall of 17 mmHg (s.e.m. = 5, n = 9) in mean arterial pressure. 2. Treatment of dogs with the angiotensin receptor antagonist, Sar1 Ile8-angiotensin II (2.5 micrograms/kg per min i.v.), or the cyclo-oxygenase inhibitor indomethacin (10 mg/kg i.v.) did not prevent the renal vasodilation and hypotension following angiotensin-converting enzyme inhibition. This suggests that these effects are neither solely due to inhibition of the renin-angiotensin system nor mediated by prostaglandins. 3. Increased urinary kinin excretion, possibly reflecting increased renal concentrations of kinins, accompanied the renal vasodilation after both captopril and renal artery occlusion. 4. The kallikrein-kinin system may play a role in the regulation of the renal vasculature in anaesthetized dogs.
Publisher: Wiley
Date: 1990
Publisher: Wiley
Date: 05-1993
Publisher: Informa UK Limited
Date: 1985
DOI: 10.3109/10641968509077210
Abstract: The hypothesis that interactions between adrenaline and adrenal cortical hormones may increase arterial blood pressure has been examined in trained dogs with chronically indwelling aortic and venous catheters. The dogs received continuous infusions for 4 days of ACTH (400 micrograms/day), or adrenaline (8 mg/day) or both ACTH and adrenaline, or saline vehicle. Compared to pre-infusion control values, ACTH raised mean arterial pressure by 14.9 +/- 2.2 mmHg by the 4th day of infusion, adrenaline infused alone had no effect (-0.2 +/- 3.9 mmHg), and ACTH and adrenaline infused together raised pressure 13.1 +/- 3.2 mmHg (not significantly different to ACTH alone). ACTH increased water consumption, Na+ and K+ excretion and creatinine clearance by the 4th day of infusion and these effects were not significantly altered when adrenaline was also infused. Thus adrenaline did not potentiate the hypertension produced by ACTH administration.
Publisher: Wiley
Date: 05-2004
DOI: 10.1111/J.1440-1681.2004.04002.X
Abstract: 1. The renal nerves constrict the renal vasculature, causing decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Whether renal haemodynamics are influenced by changes in renal nerve activity within the physiological range is a matter of debate. 2. We have identified two morphologically distinct populations of nerves within the kidney, which are differentially distributed to the renal afferent and efferent arterioles. Type I nerves almost exclusively innervate the afferent arteriole whereas type II nerves are distributed equally on the afferent and efferent arterioles. We have also demonstrated that type II nerves are immunoreactive for neuropeptide Y, whereas type I nerves are not. 3. This led us to hypothesize that, in the kidney, distinct populations of nerves innervate specific effector tissues and that these nerves may be selectively activated, setting the basis for the differential neural control of GFR. In physiological studies, we demonstrated that differential changes in glomerular capillary pressure occurred in response to graded reflex activation of the renal nerves, compatible with our hypothesis. 4. Thus, sympathetic outflow may be capable of selectively increasing or decreasing glomerular capillary pressure and, hence, GFR by differentially activating separate populations of renal nerves. This has important implications for our understanding of the neural control of body fluid balance in health and disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1983
DOI: 10.1097/00004872-198308000-00007
Abstract: The responses to 48 h of renal artery stenosis were compared in uninephrectomized, chronically-instrumented dogs with or without inhibition of angiotensin II (AII) formation by enalapril. Mean arterial pressure rose by an average of 29.9 mmHg (s.e.m. 3.5) in untreated dogs and by 14.5 mmHg (s.e.m. 2.8) in enalapril-treated dogs over the two days of stenosis. Renal artery stenosis reduced glomerular filtration rate (GFR) by 49% (s.e.m. 9) in untreated dogs and by 86% (s.e.m. 8) in enalapril-treated dogs. Compared to untreated dogs, enalapril-treated dogs also had lower renal artery pressure distal to the stenosis, drank less water and had larger rises in plasma K+ following renal artery stenosis. There were no differences in renal blood flow or urinary Na+ excretion in the two groups of dogs. Thus blockade of AII production did not prevent hypertension occurring in response to renal artery stenosis, but the rise in blood pressure was only about half that which occurred in normal dogs and GFR was much more severely reduced.
Publisher: American Physiological Society
Date: 06-1989
DOI: 10.1152/AJPRENAL.1989.256.6.F1021
Abstract: The glomeruli of kidneys subjected to reduced perfusion pressure were examined morphometrically. The left renal artery was narrowed for 30 min in anesthetized dogs with (n = 6) or without (n = 7) converting-enzyme inhibition (captopril). The kidneys were then rapidly fixed by glutaraldehyde perfusion at high flow rate. In a comparison of glomeruli of kidneys subjected to pressure reduction in captopril-treated and untreated dogs, there was significantly greater mesangial contraction in the latter, but morphometric analysis revealed no significant differences in the glomerular surface area available for filtration as evidenced by glomerular capillary volume fractions, surface areas of the filtering basement membrane between epithelial and endothelial cells, or the length densities of the glomerular epithelial slits. In a comparison of the left (pressure reduction) and right (no pressure reduction) kidneys in the captopril-treated dogs, there was no significant effect of reduction of renal perfusion pressure per se on mesangial contraction or glomerular filtration surface area when angiotensin (ANG) II formation was blocked. Thus ANG II caused mesangial cell contraction after renal artery stenosis, but this did not significantly change glomerular ultrafiltration surface area.
Publisher: AMPCo
Date: 09-2010
Publisher: AMPCo
Date: 05-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1973
DOI: 10.1097/00000658-197310000-00001
Abstract: To examine the efficacy of an enhanced intervention (EI) compared to standard care (SC) in increasing daily water intake and fluid goal adherence in children seeking treatment for retentive encopresis. Changes in beverage intake patterns and fluid adherence were examined by comparing 7-week diet diary data collected during participation in the EI to achieved data for families who had previously completed the SC. Compared to children in SC (n = 19), children in the EI (n = 18) demonstrated a significantly greater increase in daily water intake from baseline to the conclusion of treatment ( p ≤ .001), and were four and six times more likely to meet fluid targets in Phases 1 (Weeks 3-4) and 2 (Weeks 5-6) of fluid intervention, respectively (both p ≤ .001). Enhanced education and behavioral strategies were efficacious in increasing children's intake of water and improving fluid adherence. Future research should replicate the findings in a prospective randomized clinical trial to discern their effectiveness.
Publisher: American Physiological Society
Date: 03-2006
DOI: 10.1152/AJPRENAL.00275.2005
Abstract: The aim of the current study was to determine whether renal medullary oxygenation is independent of the level of cortical blood flow by testing responses to stimuli that selectively reduce blood flow in either the cortex or medulla. In anesthetized rabbits, renal arterial infusion of [Phe 2 ,Ile 3 ,Orn 8 ]-vasopressin selectively reduced medullary perfusion and Po 2 (−54 ± 24 and −50 ± 10%, respectively) but did not significantly affect cortical perfusion or tissue oxygenation. In contrast, stimulation of the renal nerves resulted in renal cortical ischemia with reductions in total renal blood flow (−76 ± 3% at 4 Hz), cortical perfusion (−57 ± 17%), and cortical Po 2 (−44 ± 12%). Medullary tissue Po 2 was reduced by −70 ± 5% at 4 Hz, despite medullary perfusion being unaffected and distal tubular sodium reabsorption being reduced (by −83.3 ± 1.2% from baseline). In anesthetized rats, in which renal perfusion pressure was maintained with an aortic constrictor, intravenous infusion of ANG II (0.5–5 μg·kg −1 ·min −1 ) dose dependently reduced cortical perfusion (up to −65 ± 3% P 0.001) and cortical Po 2 (up to −57 ± 4% P 0.05). However, medullary perfusion was only significantly reduced at the highest dose (5 μg·kg −1 ·min −1 by 29 ± 6%). Medullary perfusion was not reduced by 1 μg·kg −1 ·min −1 ANG II, but medullary Po 2 was significantly reduced (−12 ± 4%). Thus, although cortical and medullary blood flow may be independently regulated, medullary oxygenation may be compromised during moderate to severe cortical ischemia even when medullary blood flow is maintained.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1995
Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1440-1681.1996.TB02826.X
Abstract: 1. The effects of dietary sodium intake on active renin binding in the juxtaglomerular apparatus (JGA) of superficial and juxtamedullary cortex of the dog kidney were examined by quantitative in vitro autoradiography using a radiolabelled renin inhibitor [125I]-H77, which has high affinity for dog renin. 2. Changes in sodium intake resulted in marked alterations of active renin binding in the radiolabelled JGA. In comparison with the control kidney (190.8 +/- 7.7 Bq/mm3), a higher density of binding occurred in the labelled JGA of sodium-depleted kidney (277.7 +/- 6.2 Bq/mm3), while a lower density of binding was found in the labelled JGA of sodium-loaded kidney (99.3 +/- 7.4 Bq/mm3). 3. Active renin binding in the labelled JGA was significantly higher in superficial JGA than in their juxtamedullary counterparts, irrespective of sodium intake. 4. Pre-incubation with trypsin (0.5 mg/mL), a procedure known to activate prorenin, markedly increased active renin binding in the labelled JGA of control (+ approximately 35% P < 0.01) and sodium-loaded kidneys (+ approximately 75% P < 0.01), but had little effect on binding in the labelled JGA of the sodium-depleted kidney (+/- approximately 5-10% NS). The proportions of active renin as a percentage of total renin were 60, 75 and 95% in the labelled JGA of sodium-loaded, control, and sodium-depleted kidneys, respectively. 5. Emulsion microscopic autoradiography revealed that the binding was exclusively localized in the JGA, including the afferent and efferent arterioles, macula densa and extraglomerular mesangium. Labelling extended to the interlobular arteries in sodium depleted kidney. 6. These results indicate that autoradiography combined with the in vitro binding of radiolabelled renin inhibitors may provide a useful tool to measure active and prorenin renin and thereby study the physiological regulation of renin in the kidney.
Publisher: Elsevier BV
Date: 09-1999
Publisher: AMPCo
Date: 03-2012
DOI: 10.5694/MJA11.11499
Publisher: AMPCo
Date: 11-2011
DOI: 10.5694/MJA11.11252
Publisher: Wiley
Date: 08-1986
DOI: 10.1111/J.1471-4159.1986.TB04518.X
Abstract: Endogenous noradrenaline and 3,4-dihydroxyphenylethylamine (dopamine) levels were measured in different zones of the dog kidney following chronic unilateral renal denervation. In outer and inner renal cortex, and in outer medulla, greater than 95% of the tissue content of both catecholamines was contributed by renal nerves, whereas in inner medulla only nonneuronal catecholamines were found. The amounts of neuronal dopamine present in outer renal cortex were greater than would be expected for a population of solely noradrenergic nerves.
Publisher: Oxford University Press (OUP)
Date: 02-2016
DOI: 10.1016/J.AMJHYPER.2003.09.013
Abstract: The aims of this study were to examine whether combined blockade of alpha(1) and beta-adrenoceptors with carvedilol postweaning affected the development of hypertension and renal vascular narrowing in spontaneously hypertensive rats (SHR), and whether these effects on pressure and renal vascular changes persisted after treatment withdrawal. From 4 to 12 weeks of age male SHR were administered carvedilol in rat chow at 1.2 mg/g chow (low-dose) or 2.4 mg/g chow (high-dose), or were given normal chow. At 12 weeks of age, rats from each group either underwent experimentation or had treatment withdrawn and were studied at 20 weeks. On the experimental day, conscious mean arterial pressure (MAP) was measured and, as a functional test of renal vessel lumen characteristics, pressure-flow and pressure-glomerular filtration rate (pressure-GFR) relationships were determined in the maximally dilated kidney. At 12 weeks of age, SHR on low and high-dose carvedilol had significantly lower MAP than that of untreated SHR (137 +/- 3, 134 +/- 1, 152 +/- 2 mm Hg, respectively P <.001). The SHR treated with high-dose (but not low-dose) carvedilol demonstrated a steeper renal pressure-flow relationship (P <.001), and a leftward shifted (P <.01) and steeper (P <.001) pressure-GFR relationship compared with control SHR. Eight weeks after carvedilol withdrawal, there were no significant differences in MAP, pressure-flow, or pressure-GFR relationships between groups. These results suggest that postweaning alpha(1) and beta-adrenoceptor blockade with high-dose carvedilol attenuated the development of hypertension and led to a preferential reduction in preglomerular resistance (increased lumen dimensions) independent of the effects on MAP. However, treatment of SHR from 4 to 12 weeks of age with high-dose carvedilol did not lead to persistent, long-term effects on arterial pressure or renal vascular narrowing after treatment withdrawal.
Publisher: Wiley
Date: 12-1990
DOI: 10.1111/J.1440-1681.1990.TB01289.X
Abstract: 1. The effect of two doses of endothelin, 10 and 50 ng/kg per min, i.v., on glomerular filtration rate (GFR), tubular stop flow pressure and pre- and post-glomerular vascular resistance have been studied in anaesthetized rabbits. 2. Blood pressure did not change significantly in response to 10 ng/kg per min endothelin or vehicle infusion, but rose steadily during infusion of 50 ng/kg per min endothelin, increasing 11.8 +/- 2.7 mmHg by 90 min of infusion. 3. Glomerular filtration fraction (3H-inulin extraction ratio) rose and remained elevated throughout the endothelin infusion at 50 ng/kg per min. GFR did not change significantly until 70-90 min of the infusion (50 ng/kg per min) when it decreased by about 35%. No significant changes were seen at 10 ng/kg per min endothelin. 4. Sodium excretion rate rose in response to the lower dose, due to an increase in fractional sodium excretion. No changes in sodium excretion were seen at the higher dose of endothelin. 5. Glomerular capillary pressure rose significantly in response to endothelin infusion (50 ng/kg per min). 6. Renal blood flow fell progressively in response to endothelin (50 ng/kg per min), to about one-third of the pre-infusion value. 7. Renal vascular resistance increased progressively with both doses of endothelin, by about 35% at 10 ng/kg per min and about 400% at 50 ng/kg per min after 70-90 min. Preglomerular resistance increased from 1.0 +/- 0.1 to 5.0 +/- 1.9 mmHg/mL per min in response to endothelin 50 ng/kg per min. Postglomerular resistance rose from 1.0 +/- 0.1 to 5.6 +/- 2.17 mmHg/mL per min. 8. Thus endothelin infusion caused progressive renal vasoconstriction with similar magnitude increases in both pre- and postglomerular vessels. The vasoconstriction of the kidney caused by endothelin occurred at a dose which did not effect systemic blood pressure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1998
DOI: 10.1097/00004872-199816121-00008
Abstract: The aim of this study was to test the effects of exogenous endothelin-1 (ET-1) on regional kidney blood flow and renal function, and the renal haemodynamic effects of endogenous ET, in anaesthetized rabbits. ET-1 was infused into the left renal artery at 2 ng/kg/min for 30 min, then at 1 ng/kg/min. Cumulative doses of TAK-044 (0.1-3 mg/kg, i.v.) or its vehicle were given at 30-min intervals. In other rabbits, an extracorporeal circuit was established to adjust renal arterial pressure (RAP) independently of systemic arterial pressure (MAP). RAP was set at 65 mmHg, and either TAK-044 (3 mg/kg, i.v.) or its vehicle was administered. In the infused kidney ET-1 (2 ng/kg/min) reduced renal blood flow (RBFprobe 52+/-8%), cortical perfusion (37+/-7%), glomerular filtration rate (GFR 49+/-8%), urine flow (47+/-14%) and sodium excretion (49+/-13%), but not medullary perfusion (5+/-6%). No effects of ET-1 on MAP or on the contralateral kidney were observed. TAK-044 dose-dependently reversed the effects of ET-1 on RBFprobe and cortical perfusion. TAK-044 also reduced MAP (by up to 11+/-3%) and increased effective renal blood flow in the contralateral kidney (by up to 46+/-27%). In the extracorporeal circuit model, TAK-044 decreased MAP by 12+/-2% and RAP by 10+/-3%, and increased RBF by 9+/-3%. Exogenous ET-1 reduces cortical more than medullary perfusion, and reduces GFR without affecting net tubular sodium and fluid reabsorption. TAK-044 antagonizes local renal vascular responses to ET-1. Endogenous ETs appear to contribute markedly to resting renal vasomotor tone and MAP.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1997
DOI: 10.1097/00004872-199715100-00018
Abstract: To study the effects of denervation of the kidney on renal vascular resistance at maximal dilatation and renal function during the development of hypertension in the spontaneously hypertensive rat (SHR). SHR aged 6 weeks were subjected to left renal denervation or a sham-operation (n = 18 denervated, n = 13 sham). When they were aged 10 weeks, pairs of denervated and sham-operated left kidneys were perfused with 2% dextran in Tyrode's solution and pressure-flow and pressure-glomerular filtration rate (GFR) relationships at maximal vasodilation were established. The awake mean arterial blood pressure, in-vivo renal function and renal noradrenaline content were also measured. There were no significant differences between the pressure-flow relationships for denervated and sham-operated kidneys. However, there was a marked, parallel, shift leftwards in the pressure-GFR relationship (P < 0.001). Thus, the denervated kidneys commenced filtering at a lower threshold perfusion pressure than did the sham-operated ones. In-vivo renal plasma flow and GFR were significantly greater in the denervated left kidneys of SHR than they were in the contralateral kidneys. The noradrenaline content in denervated kidneys was 5 +/- 3% of that in innervated kidneys. The awake mean arterial pressure was 135 +/- 1 and 138 +/- 2 mmHg in the denervated and sham-operated groups respectively. Denervation of the kidney of SHR aged 6 weeks of age altered the pressure-GFR but not the pressure-flow relationship for these rats 4 weeks later. The results are compatible with there having been an increase in average preglomerular and a decrease in post-glomerular vessel lumen diameters. These changes suggest that the renal nerves affect the structural development of the renal vasculature in SHR.
Publisher: AMPCo
Date: 04-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1995
Abstract: Abstract Angiotensin-converting enzyme inhibitors prevent the development of vessel wall hypertrophy in some vascular beds in spontaneously hypertensive rats (SHR), but their effects on hypertrophy of renal arterial vessels have not been studied. We therefore used stereological techniques to study wall and lumen dimensions of the interlobular (cortical radial) and arcuate arteries in the kidneys of SHR (n=7), SHR treated from 4 to 10 weeks of age with enalapril (25 to 30 mg/kg per day SHR-E, n=7), and Wistar-Kyoto rats (WKY, n=7). All kidneys were perfusion-fixed at 10 weeks. Systolic blood pressure was 199±9, 139±11, and 156±8 mm Hg in the SHR, SHR-E, and WKY groups, respectively. For the interlobular arteries, the volume density of artery wall, wall-to-lumen ratio, and wall thickness in the untreated SHR were significantly greater than in the WKY (0.84±0.09 versus 0.69±0.07×10 −3 , 0.75±0.20 versus 0.53±0.08, and 13.6±3.3 versus 10.6±0.8 μm, respectively), but values in the SHR-E were similar to those in the untreated SHR (1.10±0.20×10 −3 , 0.88±0.22, and 14.0±2.6 μm, respectively). For the arcuate arteries, wall thickness and volume density were significantly greater in SHR than WKY (17.3±3.0 versus 13.9±1.7 μm and 1.63±0.51 versus 1.14±0.27×10 −3 , respectively), and values in the SHR-E (15.7±1.7 μm and 1.69±0.50×10 −3 , respectively) were not significantly different from those in SHR. Thus, enalapril treatment did not prevent vessel wall hypertrophy of both the interlobular and arcuate arteries in SHR despite the normalization of arterial pressure. These results suggest that renal arterial hypertrophy in SHR is not caused by either angiotensin II or elevated arterial pressure.
Publisher: American Physiological Society
Date: 10-2004
DOI: 10.1152/AJPREGU.00202.2004
Abstract: We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II cl ) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg·kg −1 ·h −1 ) plus ANG II (∼20 ng·kg −1 ·min −1 ), the other vehicle. Measurements were made before (room air) and during 14% O 2 . Renal blood flow decreased less during ANG II cl compared with vehicle [9 ± 1% vs. 20 ± 4%, interaction term (P GT ) 0.05], despite a similar increase in RSNA in response to 14% O 2 in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O 2 in both groups. Glomerular capillary pressure increased from 33 ± 1 to 37 ± 1 mmHg during ANG II cl and from 33 ± 2 to 35 ± 1 mmHg in the vehicle group before and during 14% O 2 , respectively (P GT 0.05). During ANG II cl , postglomerular vascular resistance was still increased in response to RSNA during 14% O 2 , demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.
Publisher: Oxford University Press (OUP)
Date: 07-1998
DOI: 10.1016/S0895-7061(98)00045-4
Abstract: To characterize the role of cytochrome P450 metabolism of fatty acids in the renal response to increased renal perfusion pressure, we tested the effects of renal arterial infusion of 17-octadecynoic acid (17-ODYA, 450 nmol/min) on renal and systemic hemodynamic, and renal excretory responses to step-wise increases in renal perfusion pressure (RPP) in anesthetized rabbits, using an extracorporeal circuit for renal autoperfusion. Inhibition of cytochrome P450-dependent fatty acid metabolism was estimated by comparing the metabolism of arachidonic acid in microsomes prepared from the kidneys of control and 17-ODYA-treated animals. Step-wise increases in RPP decreased mean arterial pressure, which previous studies have indicated is attributable to the release of a depressor hormone from the renal medulla. Elevations in RPP also increased renal blood flow and glomerular filtration rate, and the absolute and fractional excretions of urine and sodium. Intrarenal infusion of 17-ODYA reduced the metabolism of arachidonic acid to 20-hydroxyeicosatetraenoic acid by 41%, but it did not significantly influence the responses to increased renal perfusion pressure. We conclude that either the responses elicited by increased renal perfusion pressure in anesthetized rabbits do not depend on cytochrome P450-dependent fatty acid metabolism, or that cytochrome P450 activity must be inhibited by more than was achieved in the present study (41%), before functional effects on the response to increased renal perfusion pressure are observed.
Publisher: AMPCo
Date: 11-1998
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2000
Abstract: Abstract —Experimental narrowing of the main renal artery to produce hypertension increases the aorta-glomerular capillary pressure difference and vascular resistance. This article examines the hypothesis that hypertension also may be caused by structural changes that narrow intrarenal blood vessels, similarly increasing preglomerular vascular resistance and the aortic-glomerular capillary pressure gradient. There is evidence of both wall hypertrophy and lumen narrowing of the preglomerular arteries in spontaneously hypertensive rats, with increased preglomerular resistance and aortic-glomerular capillary pressure difference. We have also attempted to induce structural changes in renal-preglomerular vessels experimentally by infusing angiotensin II at low doses (0.5 to 4.5 ng/kg per minute) into the renal artery of Sprague-Dawley rats and greyhound dogs for up to 4 weeks. This angiotensin II infusion produced apparent dose-related effects on preglomerular vessel structure and hypertension. The possibility that hypertension may be induced by structural changes in preglomerular resistance vessel walls, by simulation of the hemodynamic effects of main renal artery stenosis, deserves further investigation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: Cambridge University Press (CUP)
Date: 1999
DOI: 10.1017/S0963180199801121
Abstract: Twenty years ago, Australian biomedical researchers took the first steps along a pathway toward common ground with opponents of the use of animals in science. Leaders of Australian medical research at that time saw the necessity of established science facing the ethical and political challenges that a revived antivivisectionist movement was mounting in the late 1970s and the 1980s.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1111/J.1523-1755.2005.00090.X
Abstract: Genetic noise between outbred animals can potentially be a major confounder in the use of microarray technology for gene expression profiling. The study of paired organs from the same animal offers an alternative approach (e.g., for studies of the kidney in experimental hypertension). The present study was undertaken to determine the level of genetic noise between outbred adult Sprague-Dawley (SD) rats, and to determine the effects of unilateral nephrectomy on changes in gene expression as a basis for the design of microarray studies in experimental hypertension. Male SD rats (approximately 130 g) were acclimatized before measurement of tail-cuff systolic blood pressure (SBP) for 6 control days and 4 days of saline treatment. Left kidney nephrectomy was performed, and the tissue snap-frozen in liquid nitrogen for subsequent RNA extraction. Two weeks later, SBP was measured over 4 control and 8 saline treatment days, and the remaining right kidney removed and frozen. Total RNA purification, preparation of cRNA, hybridization, and scanning of the Rat U34A Affymetrix arrays were performed, and data analyzed using MAS5 software Affymetrix Suite (v5), Bioconductor, as well as statistical methods motivated by relevant simulations. Gene expression profiles in the left control kidney were extremely consistent across animals. The expression profiles of pairs of kidneys from the same animal were, however, more similar than those of kidneys from different animals. Nephrectomy had little effect on the gene expression profiles in the time frame examined. Despite the outbred nature of the rats used in this study, they are useful for gene expression profiling comparisons. The use of paired organs from an in idual animal ensures even further genetic identity, allowing determination of genes modified by the treatment of interest.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2001
DOI: 10.1097/00004872-200107000-00017
Abstract: To compare the volumes of renomedullary interstitial cell (RMIC) lipid droplets (putative source of vasodepressor substance) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats on high and low salt diets as an indication of whether the renomedullary vasodepressor system of the SHR is defective. Ten-week-old male SHR and WKY rats received a low (0.05% w/w) or high salt (5.0%) diet for 21 days. Conscious mean arterial pressure (MAP) was measured and the renal papilla perfusion fixed with a high osmolarity fixative. Using electron microscopic stereological techniques, the volume density of lipid in RMIC (VVLipid,RMIC) and the total volumes of lipid (VLipid) and RMIC (VRMIC) in papilla were measured. MAP of SHR (high 155 +/- 3 mmHg low 151 +/- 3 mmHg) was significantly greater than WKY rats (high 126 +/- 2 mmHg low 129 +/- 2 mmHg P< 0.001), however salt diet had no significant effect on MAP. The VLipid of rats on the low salt diet was approximately 2.5 times greater than in rats on the high salt diet (P < 0.01). SHR had significantly greater VLipid than WKY rats irrespective of salt diet (P< 0.05 SHR-low 0.245 +/- 0.031 mm3, SHR-high 0.093 +/- 0.007 mm3 WKY-low 0.126 +/- 0.032 mm3, WKY-high 0.051 +/- 0.020 mm3). Similar differences were seen for VVLipid,RMIC, however VRMIC was not different between rat strains or salt diet groups. SHR and WKY rats responded similarly to the altered salt diets, and SHR demonstrated greater volumes of stored RMIC lipid droplets irrespective of the level of salt intake. These results indicate that SHR hypertension is not due to a deficiency in the amount of lipid droplets, the putative source of the renomedullary vasodepressor substance and that the renomedullary vasodepressor system of the SHR is capable of responding normally to the physiological stimulus of altered salt intake.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 26-06-2009
Publisher: American Physiological Society
Date: 10-1990
DOI: 10.1152/AJPREGU.1990.259.4.R813
Abstract: Many studies have shown that atrial natriuretic peptide (ANP) reduces mean arterial pressure (MAP) in conscious animals by lowering cardiac output (CO) with no change or even increased total peripheral resistance (TPR). Because ANP is thought to be a vasodilator, the lack of fall in TPR in conscious animals is generally considered to be due to autonomic reflex increases in vascular resistance. In the present study in conscious, trained, chronically instrumented dogs (n = 7), we measured hemodynamic and renal excretory responses to 30-min infusions of alpha-human ANP (alpha hANP 25, 50, and 100 ng.kg-1.min-1) in the presence and absence of autonomic nervous system blockade using the ganglion blocking agent pentolinium. In the absence of blockade, MAP and CO fell, whereas TPR rose with alpha hANP infusions, but these changes did not reach significance. There were significant increases in renal vascular resistance (RVR 16-25%) and mesenteric vascular resistance (MVR 14-40%). During autonomic nervous system blockade, alpha hANP caused dose-related reductions in MAP (7-12%), due to falls in CO (13-34%). Remarkably, the absence of autonomic reflex responses exposed substantial dose-related increases in TPR (5-33%). Autonomic blockade did not alter the ANP-induced increases in MVR but did abolish the rises in RVR. In summary, ANP caused vasoconstriction in mesenteric vasculature and substantial vasoconstriction in other nonrenal areas, independent of autonomic reflexes.
Publisher: Wiley
Date: 04-1988
DOI: 10.1111/J.1440-1681.1988.TB01071.X
Abstract: 1. The effects of atrial natriuretic polypeptide (ANP) on renal function were examined in renal wrap hypertensive rabbits and sham operated rabbits. 2. ANP (2 micrograms/min) induced hypotension, but did not produce significant diuresis, natriuresis or change in the glomerular filtration rate (GFR) in renal wrap hypertensive rabbits (n = 8). 3. In sham operated normotensive rabbits (n = 4), ANP induced significant diuresis (230%) and increased GFR by about 40%. 4. Thus, ANP was markedly less effective in the impaired kidneys of renal wrapped rabbits than in normal kidneys.
Publisher: Elsevier
Date: 2000
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2005
DOI: 10.1097/01.HJH.0000163155.29740.D2
Abstract: To determine the effects of chronic denervation on renal vascular structure and function in young adult spontaneously hypertensive rats (SHRs). Unilateral renal denervation (SHRUDx) or sham-operation (SHRS) was performed in SHRs at 6 weeks of age. At 10 weeks, rats were allocated to one of three procedures designed to examine renal vascular structure and function. A further group underwent bilateral renal denervation. In SHRUDx or SHRS groups, either the kidneys were perfusion-fixed for stereological estimates of artery wall and lumen dimensions or for vascular casting to determine arteriole lumen diameters, or the rats were anaesthetized for estimation of glomerular capillary pressure. Chronic unilateral renal denervation had no significant effect on the development of hypertension between 6 and 10 weeks of age, as previously reported, but resulted in luminal narrowing of the interlobular artery (denervated group 52 +/- 2 mum, sham-operated group 64 +/- 1 mum P < 0.01 for interaction between strain and treatment), without alterations in interlobular or arcuate artery wall dimensions. There were no significant effects on either afferent or efferent arteriole lumen diameters. Estimated glomerular capillary pressure was significantly lower in the denervated kidneys of SHRUDx (47 +/- 1 mmHg) compared with kidneys of the SHRS (50 +/- 1 mmHg P < 0.04). Mean arterial pressure was approximately 12 mmHg lower in the bilaterally denervated SHRs than in the sham-operated SHRs. Although bilateral denervation attenuated the development of hypertension in SHRs, unilateral denervation did not, indicating that one neurally intact kidney was sufficient to drive the normal development of SHR hypertension, but only with apparent prohypertensive compensatory changes in the denervated kidney.
Publisher: Wiley
Date: 25-07-2003
DOI: 10.1046/J.1440-1681.2003.03868.X
Abstract: 1. The neonatal reweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR). 2. We tested whether alpha1-adrenoceptor-mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR. 3. Male SHR were treated with the alpha1-adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age. 4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age. 5. These findings do not support the involvement of alpha1-adrenoceptor-mediated effects during the preweaning period in the development of hypertension in adult SHR.
Publisher: Springer Science and Business Media LLC
Date: 1976
DOI: 10.2165/00003495-197600111-00030
Abstract: In the rabbit, administration of 500 mug (+/-) propranolol into the lateral cerebral ventricle resulted in rapid leakage of drug into the blood. The drug produced a small reduction in blood pressure at 2 and 4 hours after injection but because of the rapid leakage, this could have been due to its peripheral actions. To investigate possible central mechanisms of action which were independent of peripheral effects, we tested the action of intravenously administered propranolol on the reflex rise in TPR evoked in rabbits by graded Valsalva-like manoeuvres. This was performed in unanaesthetised rabbits with Doppler flowmeters for measuring cardiac output. Graded expiratory pressures (EP) were applied to the inlet and outlet tubes of the tracheotomised animal's respiratory valve and to the cuff around their thorax and abdomen. Administration of propranolol at two levels (168 +/- 35 ng/ml, and 240 +/- 33 ng/ml) for 1 hour had no effect on slope and threshold of the EP-TPR relationship. By contrast to the minimal effects on the reflex with propranolol, the EP-related rise in TPR was attenuated by clonidine. We conclude that propranolol does not lower blood pressure in the rabbit by attenuating sympathetic constrictor activity.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2017
DOI: 10.1101/110825
Abstract: On November 18-19, 2016, the Human Frontier Science Program Organization (HFSPO) hosted a meeting of senior managers of key data resources and leaders of several major funding organizations to discuss the challenges associated with sustaining biological and biomedical (i.e., life sciences) data resources and associated infrastructure. A strong consensus emerged from the group that core data resources for the life sciences should be supported through a coordinated international effort(s) that better ensure long-term sustainability and that appropriately align funding with scientific impact. Ideally, funding for such data resources should allow for access at no charge, as is presently the usual (and preferred) mechanism. Below, the rationale for this vision is described, and some important considerations for developing a new international funding model to support core data resources for the life sciences are presented.
Publisher: American Physiological Society
Date: 08-2000
DOI: 10.1152/AJPREGU.2000.279.2.R629
Abstract: The ersity of renal arteriole diameters in different cortical regions has important consequences for control of glomerular capillary pressure. We examined whether intrarenal angiotensin II (ANG II 0.1, 1, or 5 ng · kg −1 · min −1 ) in anesthetized rabbits acts preferentially on pre- or postglomerular vessels using vascular casting. ANG II produced dose-related reductions in afferent and efferent diameters in the outer, mid, and inner cortex, without effecting arterial pressure. Afferent diameter decreased more than efferent in the outer and mid cortex ( P 0.05) but by a similar extent in juxtamedullary nephrons ( P = 0.58). Calculated efferent resistance increased more than afferent, especially in the outer cortex (127 vs. 24 units 5 ng · kg −1 · min −1 ANG II). ANG II produced significant dose-related increases in the distance between the arterioles at the entrance to the glomerular pole in all regions. Thus afferent diameter decreased more in response to ANG II, but efferent resistance rose more due to smaller resting luminal dimensions. The results also indicate that glomerular pole dimensions change in response to ANG II.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1986
Abstract: We have investigated the role of angiotensin II in the development of high blood pressure and in the maintenance of renal function during 2 weeks of one-kidney renal artery stenosis in conscious dogs. Responses to a fixed degree of inflation of a balloon cuff around the renal artery were compared in dogs with or without continuous enalapril (MK 421) treatment. In six untreated dogs, mean aortic pressure was increased by 17.1 +/- 2.0 mm Hg, due primarily to increases in total peripheral resistance with little change in cardiac output, while glomerular filtration rate, renal blood flow, renal artery pressure, and plasma renin activity were back to prestenosis levels. In seven enalapril-treated dogs mean aortic pressure was increased by 23.0 +/- 2.7 mm Hg and was not significantly different from that occurring in untreated dogs. This rise was due to increases in total peripheral resistance (10%) and cardiac output (12%). In the absence of angiotensin II, glomerular filtration rate remained low, at only 56 +/- 6% of prestenosis levels. Renal blood flow returned to normal, but the renal artery pressure remained 25% lower than control values. Thus, the main role of angiotensin II in chronic one-kidney Goldblatt hypertension does not appear to be through its pressor properties but rather through its actions in the kidney to preserve glomerular filtration. This effect on renal function persisted throughout the course of the hypertension, even when the plasma renin levels returned to normal.
Publisher: AMPCo
Date: 07-2014
DOI: 10.5694/MJA14.00347
Abstract: Health and medical research has played an important role in improving the life of Australians since before the 20th century, with many Australian researchers contributing to important advances both locally and internationally. The establishment of the National Health and Medical Research Council (NHMRC) to support research and to work to achieve the benefits of research for the community was significant. The NHMRC has also provided guidance in research and health ethics. Australian research has broadened to include basic biomedical science, clinical medicine and science, public health and health services. In October 2002, the NHMRC adopted Indigenous health research as a strategic priority. In 2013, government expenditure through the NHMRC was $852.9 million. This article highlights some important milestones in the history of health and medical research in Australia.
Publisher: Springer Science and Business Media LLC
Date: 03-2015
DOI: 10.1038/519158A
Publisher: Elsevier BV
Date: 11-1981
DOI: 10.1038/KI.1981.184
Abstract: The effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on the renal kallikrein-kinin system and renal hemodynamics was studied in anesthetised dogs for 45 min after captopril administration. ACE inhibition was confirmed by increases in blood angiotensin I (AI) and plasma renin activity and a 20-fold decrease in sensitivity of the blood pressure and renal blood flow dose-response curves to AI. Captopril (1.5 mg . kg-1, i.v.) led to an increase in renal blood flow of 56 +/- 13 ml/min-1 (P less than .01) despite a fall in mean arterial pressure of 17 +/- 5 mm Hg (P less than 0.005). Glomerular filtration rate did not change whereas the filtration fraction decreased (p less than 0.005). The hypotension and renal vasodilation were accompanied by an increase in urinary kinin excretion (P less than .025) but no acute change in circulating kinins or urinary kallikrein excretion. Urine volume and urinary sodium and potassium excretion increased. To determine the contribution of the renin-angiotensin system to these hemodynamic changes, were gave captopril to a further group of dogs during a continuous infusion of the competitive angiotensin II (AII) receptor antagonist sar1ile8-AII (2.5 micrograms/kg/min). Subsequent ACE inhibition was still associated with an increase in renal blood flow of 35 +/- 17 ml/min-1 (P less than 0.05), decrease with a mean arterial pressure by 11 +/- 4 mm Hg (P less than 0.025). These results suggest that ACE inhibition increases levels of intra-renal kinins and that decreased degradation of these tissue vasodilator peptides may contribute significantly to the acute renal vasodilation and hypotensive effect of captopril.
Publisher: Informa UK Limited
Date: 1997
DOI: 10.3109/10641969709083199
Abstract: The effects of the angiotensin II type 1 receptor antagonist TCV-116 on the wall dimensions of the interlobular and arcuate arteries have been studied. SHR rats were treated with TCV-116 between 4 and 10 weeks, at which time their kidneys were perfusion-fixed and examined using stereological techniques. TCV-116 reduced arterial pressure and left ventricle/body weight ratio, but did not reduce renal arterial wall dimensions. For both arcuate and interlobular arteries, wall density/kidney ratio was significantly greater in the TCV-116 treated SHR than in untreated SHR and wall:lumen ratio was also significantly greater for the interlobular arteries in the TCV-116 treated rats. These findings are similar to those obtained previously using enalapril, and indicate that hypertrophy of the walls of these intra-renal arteries is not secondary to the elevated arterial pressure, unlike in other vascular beds.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2001
DOI: 10.1097/00004872-200102000-00021
Abstract: To determine the effects on pre- and post-glomerular vascular resistance of adrenocorticotrophin (ACTH)-induced hypertension in rats, before and after blockade of nitric oxide formation. Four groups of Sprague-Dawley rats were studied. Measurements were made in ACTH- (Synacthen Depot, 0.25 mg/kg twice daily for 8 days) and sham-treated anaesthetized rats, before and after either Nomega-nitro-L-arginine (L-NNA, 6 mg/kg) or vehicle. Whole-kidney and single-nephron haemodynamics and function were measured. Glomerular capillary pressure was estimated from tubular stop-flow pressure measurements. Blood pressure (P < 0.001), renal blood flow (RBF, P < 0.05) and glomerular filtration rate (P < 0.01) were increased following ACTH treatment compared with sham. There were no differences in either total renal, or pre- or post-glomerular vascular resistances, but stop-flow-estimated glomerular capillary pressure was elevated (P < 0.001) as was single-nephron glomerular filtration rate (SNGFR) (P < 0.001) and single-nephron blood flow (P < 0.01 ) in the ACTH- compared to the sham-treated rats. L-NNA treatment increased blood pressure by a similar extent in both ACTH- and sham-treated rats, but reduced RBF (P < 0.05) and glomerular filtration rate (GFR) (P < 0.05) more in the ACTH group similar changes were seen in single-nephron values. L-NNA increased pre- and post-glomerular resistances to a greater extent in the ACTH group. ACTH-induced hypertension produced glomerular hypertension and hyperfiltration, which may be due to nitric oxide-related vasodilatation of the renal vasculature.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2005
Publisher: Elsevier BV
Date: 05-2002
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2000
Abstract: Abstract —The effects on the renal vasculature and on arterial blood pressure of chronic infusion of low doses of angiotensin II (Ang II) into the renal artery were studied. Sprague Dawley rats were infused continuously with Ang II (0.5, 1.5, or 4.5 ng · kg −1 · min −1 ) or vehicle into the right renal artery (contralateral nephrectomy). Intrarenal Ang II infusion for 25 days produced dose-dependent rises ( P .001) in awake mean arterial pressure (111±1, 119±5, and 130±3 mm Hg in rats receiving 0.5, 1.5, and 4.5 ng · kg −1 · min −1 Ang II, respectively) compared with 105±1 mm Hg (vehicle). Renal vessel lumen characteristics were assessed with an established, maximally dilated, isosmotic perfused kidney preparation. This revealed a small dose-dependent right shift in the pressure-flow relation ( P =0.05), as well as a dose-dependent right shift and a dose-dependent reduction in the slope of the pressure–glomerular filtration rate relation ( P =0.04 and 0.03, respectively). The effects of Ang II infusion on arterial pressure were not affected by the timing of the contralateral nephrectomy but were reduced when the contralateral kidney remained in situ. Acute losartan administration (10 mg/kg IV bolus) produced similar effects on arterial pressure in rats infused with vehicle or Ang II (4.5 ng · kg −1 · min −1 ) for 14 days, P =0.89), indicating the lack of systemic spillover of Ang II. Intraperitoneal Ang II (0.5, 1.5, or 4.5 ng · kg −1 · min −1 for 25 days) had no effect on arterial pressure. Thus, chronic intrarenal infusion of low doses of Ang II resulted in changes in the renal vasculature compatible with dose-related structural reductions in the lumen diameter of preglomerular vessels and produced dose-related increases in arterial pressure.
Publisher: Informa UK Limited
Date: 1986
DOI: 10.3109/10641968609044090
Abstract: The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervation of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 +/- 3 mmHg and 31 +/- 3 mmHg in rabbits with innervated kidneys and 7 +/- 2 mmHg and 26 +/- 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.
Publisher: AMPCo
Date: 2012
DOI: 10.5694/MJA12.N1601
Publisher: Wiley
Date: 1991
Publisher: American Physiological Society
Date: 06-2007
DOI: 10.1152/AJPRENAL.00436.2006
Abstract: Renal blood flow (RBF) can be reduced in rats and rabbits by up to 40% without significant changes in renal tissue Po 2 . We determined whether this occurs because renal oxygen consumption changes with RBF or due to some other mechanism. The relationships between RBF and renal cortical and medullary tissue Po 2 and renal oxygen metabolism were determined in the denervated kidneys of anesthetized rabbits under hypoxic, normoxic, and hyperoxic conditions. During artificial ventilation with 21% oxygen (normoxia), RBF increased 32 ± 8% during renal arterial infusion of acetylcholine and reduced 31 ± 5% during ANG II infusion. Neither infusion significantly altered arterial pressure, tissue Po 2 in the renal cortex or medulla, nor renal oxygen consumption. However, fractional oxygen extraction fell as RBF increased and the ratio of oxygen consumption to sodium reabsorption increased during ANG II infusion. Ventilation with 10% oxygen (hypoxia) significantly reduced both cortical and medullary Po 2 (60–70%), whereas ventilation with 50% and 100% oxygen (hyperoxia) increased cortical and medullary Po 2 (by 62–298 and 30–56%, respectively). However, responses to altered RBF under hypoxic and hyperoxic conditions were similar to those under normoxic conditions. Thus renal tissue Po 2 was relatively independent of RBF within a physiological range (±30%). This was not due to RBF-dependent changes in renal oxygen consumption. The observation that fractional extraction of oxygen fell with increased RBF, yet renal parenchymal Po 2 remained unchanged, supports the hypothesis that preglomerular diffusional shunting of oxygen from arteries to veins increases with increasing RBF, and so contributes to dynamic regulation of intrarenal oxygenation.
Publisher: AMPCo
Date: 12-2005
DOI: 10.5694/J.1326-5377.2005.TB00050.X
Abstract: We need a vision to attract funding increases, and it must come from the research community.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2004
DOI: 10.1097/01.HJH.0000133744.85490.9D
Abstract: There is much evidence that the medullary circulation plays a key role in regulating renal salt and water handling and, accordingly, the long-term level of arterial pressure. It has also recently become clear that various regulatory factors can affect medullary blood flow (MBF) differently from cortical blood flow (CBF). It appears likely that the influence of hormonal and neural factors on the control of arterial pressure is mediated partly through their impact on MBF. In this review, we focus on the mechanisms underlying the differential control of MBF and CBF, particularly the relative insensitivity of MBF to vasoconstrictors such as angiotensin II, endothelin-1 and the sympathetic nerves. The vascular architecture of the kidney appears to be arranged in a way that protects the renal medulla from ischaemic insults, with juxtamedullary arterioles, the source of MBF, having larger calibre than their counterparts in other kidney regions. Indeed, recent studies using vascular casting methodology suggest that juxtamedullary glomerular arterioles are not the chief regulators of MBF, which is consistent with the idea that outer medullary descending vasa recta play a key role in MBF control. Release of vasoactive paracrine factors such as nitric oxide and various eicosanoids from the vascular endothelium, and probably also from the tubular epithelium, appear to differentially modulate responses of MBF and CBF to hormonal and neural factors. The prevailing intrarenal hormonal milieu and existing haemodynamic conditions also appear to strongly modulate these responses, indicating that multiple control systems interact to regulate regional kidney blood flow at an integrative level.
Publisher: Springer Science and Business Media LLC
Date: 12-2009
DOI: 10.1038/NM1209-1346
Publisher: AMPCo
Date: 2015
DOI: 10.5694/MJA14.01683
Publisher: Portland Press Ltd.
Date: 12-1981
DOI: 10.1042/CS0610663
Abstract: 1. Mild, moderate and severe renal artery stenosis was induced in uninephrectomized conscious dogs by inflating a renal artery cuff to lower distal pressure to 60, 40 or 20 mmHg respectively. The renal artery was narrowed progressively over the next 3 days by further inflation of the cuff to relower the distal renal artery pressure to the initial values. 2. Graded progressive stenosis produced graded progressive rises in blood pressure, plasma renin activity and total renal resistance to flow over the 3 day period, followed by a return to control values 24 h after cuff deflation. 3. The rise in total renal resistance to flow was almost entirely due to the stenosis, with only small changes occurring in renal vascular resistance. 4. in moderate and severe stenosis cardiac output did not alter significantly and thus increases in blood pressure were due to increases in total peripheral resistance. in these groups the resistance to blood flow of the stenosis accounted respectively for about 36 and 26% of the rises in total peripheral resistance. Vasoconstriction of the other non-renal vascular beds accounted for the remainder of the increase in total peripheral resistance. 5. in mild stenosis the changes in both cardiac output and total peripheral resistance were variable and not statistically significant. in this group the rise in stenosis resistance was compensated by vasodilatation of the non-renal vascular beds. 6. in all groups rises in plasma renin activity and blood pressure correlated with the haemodynamic severity of the stenosis. 7. Thus the resistance to blood flow of the moderate and severe renal artery stenoses accounted for one-quarter to one-third of the increases in total peripheral resistance. The remainder of the increase in total peripheral resistance was due to vasoconstriction of nonrenal beds.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1985
Abstract: The role of angiotensin II in the development of renal wrap hypertension was studied in rabbits that underwent either bilateral renal cellophane wrap or sham operation. In half the rabbits, angiotensin II production was blocked by continuous administration of enalapril. Four weeks after renal wrapping, mean arterial pressure had risen by 48 +/- 5 mm Hg in untreated rabbits, but by only 25 +/- 4 mm Hg in enalapril-treated rabbits (p less than 0.01). Similar differences were also measured 6 weeks after wrapping. In untreated rabbits, plasma renin activity had increased fourfold 4 and 6 weeks after renal wrapping. There were no significant changes in blood pressure or plasma renin activity following sham operation. Compared with that in sham-operated rabbits, renal blood flow was reduced by 60% in the untreated rabbits 4 weeks after wrapping but by only 30% in the enalapril-treated wrapped rabbits (p less than 0.05). Renal vascular resistances were 5.5 +/- 1.7 mm Hg . ml-1 . min-1 and 1.2 +/- 0.1 mm Hg . min . ml-1 in the untreated wrapped and sham-operated rabbits respectively and 1.9 +/- 0.4 mm Hg . min . ml-1 and 0.8 +/- 1 mm Hg . min . ml-1 in the enalapril-treated wrapped and sham-operated rabbits. Renal wrapping did not alter filtration fraction in untreated rabbits, but markedly reduced it in enalapril-treated rabbits. These results suggest that angiotensin II had two major effects in rabbits after bilateral renal wrapping: it contributed substantially to the increase in blood pressure and caused renal vasoconstriction, primarily at a postglomerular site.
Publisher: Wiley
Date: 11-1987
DOI: 10.1111/J.1445-2197.1987.TB01268.X
Abstract: The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the three-dimensional folding of a 1 Mbp region of human chromosome 11 containing the β-globin genes by integrating looping interactions of the CCCTC-binding insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type-specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the β-globin locus control region (LCR) and genes. In these cells, the modeled β-globin domain folds into a globule with the LCR and the active globin genes on the periphery. In contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact position of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.
Publisher: Wiley
Date: 09-1996
DOI: 10.1111/J.1440-1681.1996.TB03074.X
Abstract: 1. There is strong evidence for a renal basis to the development of hypertension in the spontaneously hypertensive rat (SHR). Alterations of the SHR renal vasculature, including the glomerulus, may be involved in the initiation and maintenance of hypertension in this animal model. 2. The arterial walls of pre-glomerular vessels of the SHR are hypertrophied compared with WKY vessels. Unlike other vascular beds in the SHR, this hypertrophy is independent of angiotensin II (AngII). 3. Glomerular number and volume are similar between SHR and the normotensive Wistar-Kyoto (WKY) rats. These results provide no support for the theory that a reduced filtration surface area within the kidneys of the SHR contributes to the elevated blood pressure in these animals. 4. Intrarenal hypertrophy may have similar haemodynamic consequences to clipping of the main renal artery, as in Goldblatt hypertension. Further analysis of the role of pre-glomerular arterial hypertrophy is warranted to determine its involvement in the initiation and maintenance of hypertension in the SHR.
Publisher: Wiley
Date: 08-1987
DOI: 10.1111/J.1440-1681.1987.TB01885.X
Abstract: 1. Angiotensin II was infused into the renal artery of unanaesthetized dogs at 0.4 and 2.0 ng/kg per min for 40 min each. 2. Indomethacin (3 mg/kg, and 1 mg/kg per h infusion i.v.) accentuated the angiotensin II-induced falls in glomerular filtration rate, renal blood flow and urine flow rate. Indomethacin did not alter the effects of angiotensin II on Na+ or K+ excretions. 3. Aspirin (35 mg/kg p.o. 2.5 h and 0.5 h prior to experiment) did not significantly change the renal effects of angiotensin II. 4. Both aspirin and indomethacin accentuated renal vasoconstriction during briefer (5 min) angiotensin II infusion. 5. Thus indomethacin and aspirin had markedly different effects on the actions of angiotensin II in the kidney. This suggests that at least one of these drugs has actions which affect angiotensin II-mediated vasoconstriction other than via cyclooxygenase inhibition.
Publisher: Wiley
Date: 05-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1983
DOI: 10.1097/00005344-198309000-00028
Abstract: We investigated the role of prostaglandins in the renal effects of endogenous kinins in anaesthetized dogs. Endogenous kinin levels, as indicated by urinary kinin excretion, were increased by angiotensin-converting enzyme inhibition or by 10-min renal artery occlusion. Angiotensin-converting enzyme inhibition with captopril resulted in increased renal blood flow that was not prevented by prior inhibition of prostaglandin synthesis with indomethacin. The renal vasodilation after temporary renal artery occlusion was also not altered by indomethacin treatment. Thus both angiotensin-converting enzyme inhibition and renal artery occlusion caused increased kinin levels and renal vasodilation that was not dependent on prostaglandins. These results also suggest that intrarenal kinins have a role in the control of renal blood flow.
Publisher: Elsevier BV
Date: 04-1982
DOI: 10.1016/0002-9149(82)90350-2
Abstract: Angiotensin-converting enzyme kininase II reduces bradykinin metabolism in vitro and in vivo. However, consistent changes in circulating bradykinin levels after the angiotensin-converting enzyme inhibitor captopril have not been reported. The kallikrein-kinin system has been suggested to be a local hormonal system concerned with regional blood flow, and hence circulating levels may not reflect local tissue levels of kinins. Anesthetized dogs given captopril had a significant increase in urinary kinin excretion without a change in circulating bradykinin levels or in urinary kallikrein. These changes in renal kinins were accompanied by a decrease in blood pressure and renal vasodilation. The hypotension and renal vasodilation produced by captopril were not attenuated either by pretreatment with the angiotension receptor antagonist Sar1-Ileu8-angiotensin II or by reduction of endogenous prostaglandin production with indomethacin. Postischemic renal vasodilation after temporary renal artery occlusion was also associated with increased urinary kinin levels. These results demonstrate that captopril effectively inhibits renal angiotensin-converting enzyme and that the renal kallikrein-kinin system may play an important role in regulating the renal vasculature and may contribute to the renal hemodynamic effects of captopril. Many polypeptide hormone membrane receptors are self-regulated by endogenous tissue concentrations of the peptide hormone. Infusions of bradykinin into rats reduced specific bradykinin receptors. A similar decrease in bradykinin receptor numbers without change in receptor affinity was demonstrated after captopril administration. These results provide indirect evidence that angiotensin-converting enzyme/kininase inhibition by captopril increases local tissue concentration of kinins, which may contribute to the hypotensive effect.
Publisher: Wiley
Date: 30-03-2005
Publisher: Wiley
Date: 10-1980
DOI: 10.1111/J.1440-1681.1980.TB00102.X
Abstract: 1. Trained chronically-instrumented dogs were subjected to renal artery stenosis twice. A 50 mmHg stenosis pressure gradient was established while the dogs were conscious or anaethetized with pentobarbitone and prepared for renal surgery. 2. Prior to stenosis, the anaesthetized dogs had significantly higher mean arterial pressure, renal vascular resistance and plasms renin activity than when they were conscious. 3. Twenty-four hours after stenosis, when all dogs were fully conscious, significant elevations in mean arterial pressure and plasma renin activity were seen only in the dogs anaesthetized for stenosis production. Creatinine clearance over this period was also markedly less than after renal artery stenosis of conscious animals. 4. It seems likely that more severe renal artery stenosis is required to produce a given pressure gradient in anaesthetized dogs than in the conscious dogs.
Publisher: Wiley
Date: 02-1979
DOI: 10.1113/JPHYSIOL.1979.SP012656
Abstract: 1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance.
Publisher: AMPCo
Date: 12-2006
DOI: 10.5694/J.1326-5377.2006.TB00729.X
Abstract: The National Health and Medical Research Council Act 1992 (Cwlth) was amended in 2006 to streamline governance arrangements and help the National Health and Medical Research Council (NHMRC) to become a more responsive organisation and more effective at both acquisition and implementation of new knowledge. As part of the NHMRC's plans for the future, we will implement the recommendations of the Investment Review of Health and Medical Research on policy- and practice-focused research, commercialisation, and recruitment of health and research professionals to the NHMRC. The NHMRC is also improving its process for selecting and supporting the best research across biomedical, clinical, public health and health services disciplines and will develop, trial and introduce new forms of communicating evidence-based information.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1999
DOI: 10.1097/00005344-199908000-00005
Abstract: Angiotensin IV, a hexapeptide fragment (3-8) of angiotensin II metabolism, has been reported to produce vasodilatation within the renal vasculature by activation of the putative AT4 receptor. However, there are conflicting findings, with previous in vivo studies providing evidence for and against a renal vasodilator action of angiotensin IV. In this study, the renal hemodynamic responses to activation of the putative AT4 receptor were studied in anesthetized rats by left renal arterial infusion of two endogenous ligands, angiotensin IV and LVV-hemorphin-7. Angiotensin IV (10, 100, and 1,000 pmol/min) infusion caused dose-dependent reductions in blood flow to the infused kidney, which were abolished by pretreatment with losartan. In respect to this effect, angiotensin IV was approximately 300-fold less potent than angiotensin II. There were no significant effects of angiotensin IV on mean arterial pressure, heart rate, or blood flow to the noninfused kidney. Intrarenal infusion of LVV-hemorphin-7 (10, 100, and 1,000 pmol/min) had no significant effect on renal blood flow in the infused and noninfused kidneys, or on mean arterial pressure or heart rate. These results provide no evidence for a renal vasodilatory action of angiotensin IV or LVV-hemorphin-7. On the contrary, intrarenal angiotensin IV infusion produced vasoconstriction of the renal vasculature, mediated by activation of AT1 receptors. These observations provide evidence against a vasodilatory role of putative AT4 receptors in the rat kidney.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1991
Abstract: Renal perfusion was increased in anesthetized rabbits and dogs by using an extracorporeal circuit. When left kidney perfusion pressure was raised in rabbits (145-240 mm Hg), arterial pressure fell by 1.34 +/- 0.20 mm Hg/min. Pretreatment of the rabbits with 2-bromoethylamine hydrobromide, which destroyed the renal medulla, abolished the fall in arterial pressure (-0.08 +/- 0.08 mm Hg/min) in response to increased renal perfusion pressure. In dogs (with blockade of autonomic ganglia by pentolinium, converting enzyme inhibition [captopril/enalaprilat], and surgical renal denervation), increasing renal perfusion pressure to 170-220 mm Hg resulted in a fall in arterial pressure by 0.32 +/- 0.03 mm Hg/min (or by 28.9 +/- 3.1 mm Hg over a 90-minute period). Mean arterial pressure did not change significantly in identically prepared dogs not subjected to increased renal perfusion pressure, whereas pretreatment of dogs with bromoethylamine abolished the hypotensive response to increased renal perfusion pressure. Thus, the hypotensive response to increased renal perfusion was dependent on the presence of an intact renal medulla, but hypotension still occurred in the presence of converting enzyme inhibition, autonomic ganglion blockade, and renal denervation. The results provide in vivo evidence in two species that a vasodepressor factor from the renal medulla is released in response to increased renal perfusion.
Publisher: Elsevier BV
Date: 06-2007
Publisher: AMPCo
Date: 08-1997
Publisher: AMPCo
Date: 04-1996
DOI: 10.5694/J.1326-5377.1996.TB122098.X
Abstract: Genetic/genomic testing (GGT) are useful tools for improving health and preventing diseases. Still, since GGT deals with sensitive personal information that could significantly impact a patient's life or that of their family, it becomes imperative to consider Ethical, Legal and Social Implications (ELSI). Thus, ELSI studies aim to identify and address concerns raised by genomic research that could affect in iduals, their family, and society. However, there are quantitative and qualitative discrepancies in the literature to describe the elements that provide content to the ELSI studies and such problems may result in patient misinformation and harmful choices. We analyzed the major international documents published by international organizations to specify the parameters that define ELSI and the recognized criteria for GGT, which may prove useful for researchers, health professionals and policymakers. First, we defined the parameters of the ethical, legal and social fields in GGT to avoid ambiguities when using the acronym ELSI. Then, we selected nine documents from 44 relevant publications by international organizations related to genomic medicine. We identified 29 ELSI sub-criteria concerning to GGT, which were organized and grouped within 10 minimum criteria: two from the ethical field, four from the legal field and four from the social field. An additional analysis of the number of appearances of these 29 sub-criteria in the analyzed documents allowed us to order them and to determine 7 priority criteria for starting to evaluate and propose national regulations for GGT. We propose that the ELSI criteria identified herein could serve as a starting point to formulate national regulation on personalized genomic medicine, ensuring consistency with international bioethical requirements.
Publisher: Wiley
Date: 1991
DOI: 10.1111/J.1440-1681.1991.TB01372.X
Abstract: 1. Evidence from experiments in conscious, instrumented dogs shows that hypertension from renal artery stenosis is due to: (i) the stimulus, the mechanical resistance of the stenosis and (ii) the secondary responses to this, especially angiotensin II (initially) and cardiovascular hypertrophy. 2. The hydraulic resistance of the stenosis is responsible for about 20-25% of the rise in blood pressure. 3. Angiotensin II is initially the most important secondary response to the stenosis. Within days, however, other as yet undetermined factors become dominant in the maintenance of the hypertension. The most important of these factors is probably cardiovascular hypertrophy. 4. These secondary factors are homeostatic, in that they mitigate the effects of stenosis on renal function.
Publisher: Wiley
Date: 26-04-2007
DOI: 10.1111/J.1440-1681.2007.04634.X
Abstract: 1. Pathological changes to the kidney, such as vascular remodelling, have been found in several models of hypertension and may contribute to the maintenance of hypertension or confer susceptibility to redeveloping hypertension after the original prohypertensive stimulus is withdrawn. 2. To investigate whether noradrenaline-induced hypertension induces persistent, functionally important changes to the kidney, the acute pressure-natriuresis relationship was characterized in anaesthetized rats under controlled neural and hormonal conditions following chronic (14 days) intravenous infusion of noradrenaline (48 microg/kg per h) or vehicle (0.04 mg/mL ascorbic acid and 0.156 mg/mL NaH2PO4 2 H2O in 10 IU/mL heparinized saline). 3. Conscious mean arterial pressure was significantly elevated by infusion of noradrenaline at 48 microg/kg per h (+10 +/- 2 mmHg at Day 14 P < 0.01 vs vehicle group). The acute relationships between arterial pressure and renal blood flow, glomerular filtration rate, Na+ excretion and urine flow were not significantly different between the noradrenaline- and vehicle-infused rats immediately after termination of noradrenaline infusion. 4. In summary, chronic intravenous noradrenaline infusion did not cause persistent changes in renal function, indicating that, in contrast with many models of hypertension, this model does not induce underlying prohypertensive changes to the kidney.
Publisher: Wiley
Date: 09-1995
DOI: 10.1111/J.1476-5381.1995.TB16373.X
Abstract: 1. We tested the renal effects of the alpha 2-adrenoceptor agonists, rilmenidine and guanabenz and the antagonists, 2-methoxyidazoxan and idazoxan, in conscious dogs. Our aim was to test the hypothesis that putative imidazoline (I) receptors influence renal function. We reasoned that since rilmenidine and guanabenz are selective for I1- and I2-binding sites respectively, an influence of one of these receptive sites on renal function would be reflected in qualitative differences between the effects of these agents. Moreover, effects mediated by putative I-receptors should be relatively resistant to antagonism by the selective alpha 2-adrenoceptor antagonist, 2-methoxyidazoxan. Since the effects of these drugs on renal function could be mediated in the central nervous system or periphery, the dogs were studied under both normal and ganglion-blocked conditions. 2. In dogs with intact autonomic reflexes, 2-methoxyidazoxan (15 micrograms kg-1 plus 0.6 micrograms kg-1 min-1) produced effects consistent with a generalized increase in sympathetic drive, including increases in mean arterial pressure and plasma renin activity, and a reduction in sodium excretion. In ganglion-blocked dogs, 2-methoxyidazoxan reduced sodium excretion but had no discernible effect on systemic or renal haemodynamics. We conclude that an alpha 2-adrenoceptor-mediated mechanism in the central nervous system tonically inhibits sympathetic drive in the conscious dog. 3. In ganglion-blocked dogs idazoxan (3-300 micrograms kg-1) dose-dependently increased arterial pressure. This was not abolished by concomitant administration of 2-methoxyidazoxan (0.3-30 micrograms kg-1). The pressor effect of idazoxan is therefore probably mediated by an agonist action at alpha 1-adrenoceptors. 4. The effects of infusions of rilmenidine (0.1-1.0 mg kg-1) and guanabenz (10-100 micrograms kg-1) were indistinguishable. They comprised dose-dependent increases in mean arterial pressure, urine excretion, and glomerular filtration rate (the latter in ganglion blocked dogs only), and dose-dependent reductions in heart rate, renal blood flow and sodium excretion (only in dogs with intact autonomic reflexes). All of these effects were antagonized by 2-methoxyidazoxan. 5. We conclude that the renal effects of rilmenidine and guanabenz infusions in conscious dogs are predominantly, if not completely, attributable to activation of alpha 2-adrenoceptors. Our results do not support the hypothesis that putative I-receptors contribute towards the renal effects of these agents.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2005
DOI: 10.1097/01.HJH.0000166839.63312.29
Abstract: To investigate the role of endothelin in noradrenaline-induced hypertension in rats. The dose-response relationship of chronic noradrenaline infusion on arterial pressure was characterized to identify a dose that would produce sustained hypertension, and the effect of combined endothelin ETA and ETB receptor blockade (TAK-044) on the response to this dose was then examined. Noradrenaline (or vehicle) was infused intravenously at 1 (subpressor acutely), 24 or 48 microg/kg per h (acute pressor response of 9 +/- 1 and 11 +/- 1 mmHg, respectively) for a 14-day infusion, and blood pressure was measured by radiotelemetry. Noradrenaline infusion at 1 microg/kg per h did not produce a 'slow pressor' rise in blood pressure. During noradrenaline infusions at 24 and 48 microg/kg per h, mean arterial pressure peaked initially on days 2-3 (+10 +/- 1 and 14 +/- 2 mmHg, respectively P < 0.01), fell towards basal levels after day 3, and then began to rise again at days 5-6 only with 48 microg/kg per h, being 10 +/- 1 mmHg above control levels at days 13-14 (P < 0.05). TAK-044 treatment did not alter the magnitude of the initial (13 +/- 1 mmHg) or eventual (12 +/- 2 mmHg) rise in blood pressure achieved in response to 14 days' infusion of noradrenaline at 48 microg/kg per h, but abolished the transient fall. Chronic noradrenaline infusion at acutely pressor doses leads either to a transient blood pressure elevation at a moderate dose, or to a triphasic but sustained hypertension at a higher dose, with a temporary escape from the hypertension apparently mediated by endothelin.
Publisher: S. Karger AG
Date: 28-01-2008
DOI: 10.1159/000114203
Abstract: i Background/Aims: /i The validity of fluorescence optodes for measurement of renal cortical tissue oxygen tension was tested by comparison with Clark electrodes. i Methods: /i We varied renal blood flow and inspired O sub /sub content in anaesthetized rabbits while simultaneously measuring cortical tissue oxygen tension. i Results: /i Cortical oxygen tension varied with inspired O sub /sub content. Fluorescence optode measurements were more tightly distributed than those from a Clark electrode. Cumulative frequency distributions for fluorescence optodes were shifted to the left of those for Clark electrodes. The slope of the relationship between oxygen tension in arterial blood and cortical tissue was less for the fluorescence optode than the Clark electrode. Cortical tissue oxygen tension measurements by these two methods were correlated (r sup /sup = 0.32 p 0.001), with no fixed bias but considerable proportional bias. Thus, the slope of the relationship between the two measurements was less than unity (0.57 [0.50–0.69]). i Conclusion: /i Cortical oxygen tension values from fluorescence optodes are less variable but proportionally less than those from Clark electrodes. Theoretical considerations suggest that true interstitial oxygen tension lies somewhere between values provided by the two techniques. Nevertheless, the lesser variability of the fluorescence optode technique may aid detection of physiologically significant changes in intrarenal oxygenation.
Publisher: Wiley
Date: 12-1981
DOI: 10.1113/JPHYSIOL.1981.SP013969
Abstract: 1. The renal haemodynamic and glomerular filtration rate (G.F.R.) responses to intravenous and intrarenal infusions of noradrenaline were studied in conscious dogs, either with or without prior blockade of angiotensin II formation with teprotide. 2. Infusion noradrenaline by either route resulted in dose-related rises in plasma renin activity. 3. Pretreatment with teprotide reduced the rise in mean arterial pressure and abolished the rise in G.F.R. seen during intravenous infusions of noradrenaline (0.1, 0.2 and 0.4 microgram/kg . min). Noradrenaline also reduced filtration fraction more after teprotide pretreatment. 4. Renal blood flow rose and renal vascular resistance fell in response to I.V. noradrenaline infusions. This renal vasodilatation was unaffected by pretreatment of the dogs with teprotide, indomethacin or DL-propranolol. However after pentolinium pretreatment, I.V. noradrenaline infusion caused a dose-related renal vasoconstriction. 5. Infusion of noradrenaline into the renal artery (0.02, 0.05 and 0.1 microgram/kg . min) resulted in rises in mean arterial pressure and G.F.R. which were abolished by teprotide pretreatment. Filtration fraction rose when noradrenaline was administered alone but fell when it was infused after teprotide treatment. 6. Thus angiotensin II formed as the result of increased renin release acted to maintain G.F.R. and filtration fraction during noradrenaline infusion. In addition, I.V. noradrenaline infusions in conscious dogs caused reflex vasodilatation of the renal vasculature.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1995
DOI: 10.1097/00005344-199510000-00001
Abstract: Endothelin (2, 5, and 10 pmol/kg/min) was infused into the renal artery of conscious dogs, producing graded and progressive reductions in renal blood flow (RBF) without initial vasodilatation, parallel reductions in glomerular filtration rate (GFR), and reduced Na+ excretion, but little change in urine flow. Pretreatment of the dogs with either ibuprofen (20 mg/kg orally) or aspirin (30 mg/kg p.o.) did not significantly alter the effects of endothelin (5 pmol/kg/min) on RBF, GFR, or Na+ excretion. However, endothelin caused antidiuresis in these cyclooxygenase-inhibited dogs, indicating that the effects of endothelin on water reabsorption were prostanoid mediated. Treatment with captopril (1.5 mg/kg + 0.5 mg/kg/h) did not significantly alter any of the responses to endothelin. The local effects of endothelin in the kidneys of conscious dogs were vasoconstriction and reduced Na+ excretion which were not mediated or modified by either angiotensin II or prostanoids.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2002
DOI: 10.1681/ASN.V13127
Publisher: Elsevier BV
Date: 05-1998
Publisher: American Physiological Society
Date: 03-1992
DOI: 10.1152/AJPRENAL.1992.262.3.F367
Abstract: To study the effects of angiotensin II on afferent and efferent arteriole diameters and on intraglomerular dimensions, angiotensin II (20 ng.kg-1.min-1) or saline vehicle was infused intravenously for 20 min into anesthetized rabbits pretreated with enalapril. Both kidneys were perfusion fixed (glutaraldehyde), and vascular casts were made of the right kidneys using methacrylate. Morphometric analysis of the left kidneys using transmission electron microscopy revealed no significant effects of angiotensin II within the glomerulus, including the degree of mesangial contraction. The diameters of the afferent and efferent arteriole casts from the right kidneys were measured at 20, 50, and 75 microns from the glomerulus by scanning electron microscopy. In the outer cortex the mean diameters of the afferent and efferent arterioles were 14.1 +/- 0.8 and 9.7 +/- 0.5 microns, respectively, in the angiotensin II-infused rabbits, significantly less than in the control (vehicle) rabbits, 17.0 +/- 0.7 microns (P less than 0.001) and 10.7 +/- 0.4 microns (P less than 0.005), respectively. Calculation of the relative changes in vascular resistance, however, indicated that the effects of angiotensin II on efferent arteriole resistance (average difference 2.4 +/- 1.2 units/microns) were significantly greater per unit length than the effects on afferent arteriole resistance (average difference 0.9 +/- 0.3 units/microns). Thus infused angiotensin II caused greater reduction in afferent arteriolar diameter than in efferent, but the calculated increase in vascular resistance per micron was greater in efferent vessels due to their smaller resting diameter.
Publisher: Wiley
Date: 1994
DOI: 10.1111/J.1440-1681.1994.TB02434.X
Abstract: 1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits. 2. A low dose of ANP (0.05 microgram/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension. 3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 +/- 3.11 mumol/min in response to ANP (approximately 55%, P < 0.05) compared to 0.84 +/- 0.59 mumol/min (approximately 28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 +/- 29.9 mumol/min (approximately 60%, P < 0.05) but not in innervated kidneys. 4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P < 0.05). 5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre-glomerular vascular resistance fell in denervated kidneys during ANP infusion. 6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium. 7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.
Publisher: American Physiological Society
Date: 11-1975
DOI: 10.1152/JAPPL.1975.39.5.843
Abstract: An arterial catheter-bearing external conductivity electrodes and a thermistor was used for measurement of lung thermal volume (LTV) by the double-indicator method. Ten milliliters of 3% saline at room temperature were injected, dilution curves measured, and LTV calculated as mean transit time difference, less thermistor time constant, times cardiac output (CO). Comparisons were made, in dogs, between LTV, pulmonary extravascular lung water with Evans blue and tritiated water (PEVWtho), and weighed lung water (WLW). Pulmonary edema was induced with dextran and epinephrine. CO was measured by thermodilution in both the pulmonary artery (PA) and aorta (AO) and dye dilution in the AO. CO from dye dilution was compared with thermodilution (aortic detection) to detect irreversible loss of thermal indicator. Comparisons showed good correspondence of dye and thermal curves (Y = 0.91X - 0.16 1/min r = 0.93). LTV is about 120% of WLW in near normal lungs, 90% of WLW in extreme edema. PEVWtho was 60–70% WLW.
Publisher: Elsevier BV
Date: 10-1992
DOI: 10.1016/0165-1838(92)90206-V
Abstract: Two structurally distinct types of sympathetic axon (Type I and Type II) have recently been identified in the renal cortex of the rat and the rabbit. This study describes the distribution and density of the neuroeffector junctions made by these two types of axon on the different tissues from the juxtaglomerular region of the rabbit renal cortex. Immunohistochemical studies showed that tyrosine hydroxylase-positive axons were located only in regions adjacent to the arteries and arterioles in the renal cortex. Ultrastructural studies of the juxtaglomerular region indicated that both types of axon formed junctions on vascular smooth muscle cells, epithelial cells of proximal tubules and renin-secreting granular epithelioid cells. The density of neuromuscular junctions (18 x 10(3)/mm2 of vessel surface) was more than twice as high on the afferent arteriole as on the efferent arteriole or proximal tubules immediately adjacent to the glomerular arterioles (both about 6 x 10(3)/mm2). The junction density on granular epithelioid cells was much lower (about 2 x 10(3)/mm2) and were rarely observed on the distal tubule. Afferent arterioles preferentially received junctions from Type I axons at a relatively high density (14.2 x 10(3)/mm2) whereas junctions formed by Type II axons were less selectively distributed and occurred at lower densities on all other tissues (range, 1-6.3 x 10(3)/mm2). Presynaptic membrane specialisations were identified only at junctions on arterioles and granular epithelioid cells and occurred more frequently at Type I than at Type II junctions. The data suggest that the predominant effect of the sympathetic innervation in the juxtaglomerular region of the renal cortex is on the afferent arteriole and that the two axon types within the kidney may have different functions.
Publisher: AMPCo
Date: 12-2010
Publisher: Elsevier BV
Date: 09-1997
DOI: 10.1016/S1056-8719(97)00046-4
Abstract: To test the validity of transit-time ultrasound flowmetry for chronic measurement of renal blood flow in dogs, we compared this method with the renal clearance of para-aminohippuric acid (CPAH) (corrected for hematocrit), and with direct volumetric measurements. When flow-probes were implanted without silastic sheeting to stabilize the implant, there was significant disparity between the (within-dog) mean levels of renal blood flow estimated by flow-probe and CPAH. In contrast, when the flow-probe implants were stabilized with silicone sheeting, there was close agreement in each dog between the flow rates measured by the two methods. When flow-probes were calibrated volumetrically in situ, there was a close linear relationship between flow derived from the flow-probe and that measured volumetrically (r = 0.98 +/- 0.02). We conclude that valid, chronic measurement of renal blood flow in dogs can be achieved using transit-time ultrasound flowmetry, provided the implant is stabilized with silicone sheeting.
Publisher: Springer Science and Business Media LLC
Date: 15-11-1999
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-06-2015
DOI: 10.1126/SCITRANSLMED.AAB0194
Abstract: Human-genomics programs work together worldwide to speed the translation of genomic medicine to the clinic.
Publisher: Elsevier BV
Date: 07-1983
DOI: 10.1016/S0024-3205(83)80005-8
Abstract: The effects of denervation of alpha 2 adrenoceptor binding sites were examined in canine arteries and veins. Denervation of the lower abdominal aorta, renal and femoral arteries and femoral veins marked reduced vessel norepinephrine concentrations. Denervation had little effect on the concentration of alpha 2 adrenoceptor binding sites or the affinity of (3H)yohimbine for these sites. The apparent lack of any significant reduction in receptor binding sites suggests that the majority of these sites are located on smooth muscle cells of blood vessels. The failure of any appreciable rise in receptor concentration following denervation is consistent with the hypothesis from functional studies that postsynaptic alpha 2 adrenoceptors on blood vessels are located extra-synaptically and hence not influenced by neurally released norepinephrine.
Publisher: Wiley
Date: 08-1987
DOI: 10.1111/J.1440-1681.1987.TB01886.X
Abstract: 1. The effects of five different non-steroidal anti-inflammatory drugs (NSAID) on the renal blood flow responses to arachidonate were compared. 2. Arachidonate (5-200 micrograms/kg) injected into the renal arteries of conscious dogs caused dose-related renal vasodilatation with no systemic effects. 3. Aspirin (35 mg/kg), phenylbutazone (12 mg/kg) and ibuprofen (25 mg/kg) all markedly reduced arachidonate-induced renal vasodilatation. 4. In contrast, neither indomethacin (3 mg/kg) or its related drug sulindac sulphide (6 mg/kg) significantly reduced arachidonate-induced renal vasodilatation. 5. All NSAID abolished the hypotensive response to intravenous injection of arachidonate (10 mg). 6. Thus, indomethacin and sulindac did not block the effects of renal artery injections of arachidonate but did abolish the systemic effects. Aspirin, phenylbutazone and ibuprofen greatly reduced responses to both renal artery and intravenous arachidonate. 7. Indomethacin and aspirin both reduced the production of prostaglandin E2 and 6-keto-PGF1 alpha by dog renal cortical microsomes in vitro. 8. Thus, indomethacin and sulindac had different effects to other NSAID on arachidonate-induced renal vasodilatation. The results are compatible with the hypothesis that some sites of prostaglandin production in the kidneys of conscious dogs may be relatively resistant to inhibition by indomethacin and sulindac.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2001
DOI: 10.1097/00004872-200108000-00020
Abstract: To characterize the in vivo vascular properties of the spontaneously hypertensive rat (SHR) renal vascular bed by examining vascular conductance/resistance responsiveness to vasoactive agents in vivo and determining whether the filtration surface area of glomerular capillaries is reduced. in vivo renal blood flow responses to intrarenally administered angiotensin II, phenylephrine and acetylcholine were compared in 10-week-old SHR and Wistar-Kyoto (WKY) rats using a wide range of doses from near threshold to near maximal effect. Unbiased stereological techniques and high-resolution light microscopy were used to estimate the surface area and length of glomerular capillaries, and evidence of capillary damage. The SHR renal bed demonstrated significantly enhanced dose-vascular resistance responses to vasoconstrictors. For vascular conductance and calculated radius of resistance vessels, the SHR curves were significantly lower across the full dilator-constrictor range examined, but the dose-related changes were similar to those of WKY rats. There were only modest enhancements of the renal blood flow responses in the SHR, evident only when renal blood flow was reduced by more than 50% SHR and WKY rats did not differ in mean glomerular capillary surface area (0.13+/-0.02 mm2 and 0.14+/-0.02 mm2, respectively) or length (5.76+/-0.85 mm and 5.48+/-0.90 mm, respectively) nor was there evidence of glomerular capillary damage in either strain. The renal vascular bed of the SHR in vivo exhibits reduced vascular conductance across a wide vasomotor range, compatible with findings in other vascular beds. We have further shown no evidence of reduced glomerular capillary surface area or damage. These findings are compatible with the hypothesis that the reduced conductance of the SHR pre-glomerular vasculature increases the aorta-capillary pressure gradient thus protecting the glomerular capillaries from systemic hypertension at this age.
Publisher: AMPCo
Date: 12-1997
DOI: 10.5694/J.1326-5377.1997.TB138911.X
Abstract: Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy and asthma risk in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) and paired infant stool (n = 172) s les, we identify four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs) that relate to prenatal maternal health and exposures and infant serum immunoglobulin E (IgE) status at 1 year. Variance in bacteria shared between mother and infant pairs relate to VCs, maternal allergy/asthma status, and infant IgE levels. Heritable bacterial gene pathways associated with infant IgE include fatty acid synthesis and histamine and tryptophan degradation. In vitro, vertically transmitted Lactobacillus jensenii strains induce immunosuppressive phenotypes on human antigen-presenting cells. Murine supplementation with L. jensenii reduces lung eosinophils, neutrophilic expansion, and the proportion of interleukin-4 (IL-4)
Publisher: American Physiological Society
Date: 06-2010
DOI: 10.1152/AJPRENAL.00049.2010
Abstract: The extent to which a reduced nephron endowment contributes to hypertension and renal disease is confounded in models created by intrauterine insults that also demonstrate other phenotypes. Furthermore, recent data suggest that a reduced nephron endowment provides the “first hit” and simply increases the susceptibility to injurious stimuli. Thus we examined nephron number, glomerular volume, conscious mean arterial pressure (MAP), and renal function in a genetic model of reduced nephron endowment before and after a high-salt (5%) diet. One-yr-old glial cell line-derived neurotrophic factor wild-type (WT) mice, heterozygous (HET) mice born with two kidneys (HET2K), and HET mice born with one kidney (HET1K) were used. Nephron number was 25% lower in HET2K and 65% lower in HET1K than WT mice. Glomeruli hypertrophied in both HET groups by 33%, resulting in total glomerular volumes that were similar between HET2K and WT mice but remained 50% lower in HET1K mice. On a normal-salt diet, 24-h MAP was not different between WT, HET2K, and HET1K mice (102 ± 1, 103 ± 1, and 102 ± 2 mmHg). On a high-salt diet, MAP increased 9.1 ± 1.9 mmHg in HET1K mice ( P 0.05) and 5.4 ± 0.9 mmHg in HET2K mice ( P 0.05) and did not change significantly in WT mice. Creatinine clearance was 60% higher in WT mice but 30% lower in HET2K and HET1K mice fed a high-salt diet than in controls maintained on a normal-salt diet. Thus a reduction in nephron number (or total glomerular volume) alone does not lead to hypertension or kidney disease in aged mice, but exposure to high salt uncovers a hypertensive and renal phenotype.
Publisher: American Physiological Society
Date: 03-2009
DOI: 10.1152/AJPRENAL.90359.2008
Abstract: We examined whether deficits in glomerular capillary surface area associated with a congenital nephron deficit could be corrected by glomerular hypertrophy. Using unbiased stereological techniques, we examined the time course and mode of glomerular hypertrophy in mice lacking one allele for glial cell line-derived neurotrophic factor (GDNF). These GDNF heterozygous (Het) mice are born with ∼30% less nephrons than wild-type (WT) littermates. An additional group of GDNF Het mice received the angiotensin type 1 (AT 1 )-receptor antagonist candesartan (Cand 10 mg·kg −1 ·day −1 ) from 5 wk of age to determine the role of AT 1 receptors in the compensatory hypertrophy. At 10 wk of age, the total volume of renal corpuscles, glomerular capillary surface area, and length of glomerular capillaries in the kidneys of GDNF Het mice were all markedly (∼45%) less than that of WT mice ( P 0.001). However, by 30 wk, and persisting at 60 wk of age, GDNF Het and WT mice did not significantly differ in any of these parameters. Furthermore, conscious 24-h mean arterial pressure (MAP) did not differ between GDNF Het and WT mice at any time point. MAP of GDNF Het-Cand mice was 20–30 mmHg less than that of GDNF Het-vehicle mice at all three ages, but Cand treatment did not significantly alter glomerular capillary dimensions. In conclusion, we have demonstrated that the deficit in glomerular capillary surface area associated with a congenital nephron deficit can be corrected for in adulthood by an increase in the total length of glomerular capillaries. This process does not require AT 1 receptor activation.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.AUTNEU.2006.08.003
Abstract: The influence of endogenous endothelins on the neural control of renal function is poorly understood. We therefore studied the effects of endothelin blockade (combined ET(A) and ET(B) receptor antagonism using TAK-044) on the acute and prolonged effects of renal nerve stimulation in rabbits, measuring renal blood flow, glomerular filtration rate (GFR), urine flow and sodium excretion. Brief (3 min) stimulation over 0.5-8 Hz produced frequency-dependent reductions in total renal blood flow, cortical blood flow and, less markedly, medullary blood flow. TAK-044 did not significantly alter basal total renal blood flow or cortical blood flow, or their responses to nerve stimulation, but significantly increased basal medullary blood flow (P<0.01) and increased the slope of the stimulation frequency-medullary blood flow relationship (P<0.05). Prolonged (20 min) stimulation at 0, 0.5 and 2 Hz produced frequency-dependent reductions in total renal blood flow, GFR, urine flow and sodium excretion, but not medullary blood flow. Pretreatment with TAK-044 did not significantly alter these responses. Thus, endogenous endothelins do not appear to either augment or lessen the effects of renal nerve activation on total renal blood flow, cortical blood flow, GFR or sodium excretion. The apparent ability of TAK-044 to enhance medullary blood flow responses to renal nerve stimulation may reflect an action of endogenous endothelins to blunt neurally mediated vasoconstriction in the medullary circulation. Alternatively, it may simply be secondary to the effects of endogenous endothelins on basal medullary blood flow.
Publisher: Canadian Science Publishing
Date: 08-1987
DOI: 10.1139/Y87-272
Abstract: The present review considers evidence that in chronic hypertension, hypertrophy of the muscles of the resistance vessels and left ventricle (LV) accounts for their intrinsic properties as haemodynamic lifiers. In spontaneously hypertensive rats (SHR) there is early hypertrophy of both vessels and LV, suggesting that they may initiate hypertension slow development of α-adrenoceptors may contribute to the early preponderance of the LV lifier. In human hypertension LV hypertrophy occurs in most patients, including a high proportion of mild hypertensives. In Goldblatt one-kidney hypertension the stenosis resistance, which is the initiating cause, accounts for 25% of the rise in blood pressure throughout, with 75% initially due to systemic constrictor action of angiotensin II and later due to the lifier properties of the hypertrophied heart and vessels. The cardiovascular lifiers must be important in all chronic hypertension, so that if hypertrophy can be reversed, detection of the initiating mechanism should be easier. Studies in patients indicate that drug therapy can reverse hypertrophy and that subsequent redevelopment of hypertension is markedly slowed. We postulate an intrinsic disturbance of muscle performance in all primary hypertension, which may be triggered through the sympathetic nervous system in some patients and through altered cation transport in others.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1974
DOI: 10.1097/00000658-197407000-00016
Abstract: The effects of acute normovolemic hemodilution on hemodynamics, oxygen transport, tissue perfusion and blood volume were studied. The subjects were four patients undergoing total hip replacement with prebleeding and hemodilution under fluoroxene and nitrous oxide anesthesia. The hematocrit was reduced to 29% and 21% by bleeding in two steps with simultaneous infusion of plasmanate and lactated Ringer's solution. The major compensation was a rise in CO to 123% and 136%. Systemic oxygen transport (COX arterial O(2) content) was only slightly reduced and the arteriovenous oxygen difference decreased. Tissue perfusion remained excellent. Blood volume was slightly expanded. The procedure was well tolerated by this group of selected patients, and homologous blood utilization was markedly reduced.
Publisher: Elsevier BV
Date: 10-1996
DOI: 10.1016/0165-1838(96)00060-4
Abstract: We have stimulated the rostral ventrolateral medulla of the central nervous system to increase renal sympathetic nerve activity (RSNA), and measured the effect on renal blood flow, glomerular filtration rate, and urinary excretion. Increases in RSNA were produced by infusion of 0.02 M glutamate at a rate of 30-50 nl/min into the subretrofacial nucleus for 40 min, in 10 urethane anaesthetized rabbits. Changes in RSNA were quantified as the mean nerve activity per 1 s period and as the frequency and litude of in idual discharges (reflecting the number of activated nerve fibres). Glutamate infusion increased RSNA 59 +/- 11% over control levels. This was predominantly due to a 65 +/- 15% increase in the frequency of discharges (3.0 +/- 0.35 to 4.6 +/- 0.4 Hz), rather than the litude of the discharges (+9 +/- 3% over control). The effects of these changes on the kidney were made against data collected in the last 20 min of the infusion and the 40 min pre-and post-stimulation periods, when arterial pressure and heart rate were unchanged from control levels. Renal blood flow fell significantly from 31.3 +/- 4.5 to 17.7 +/- 5.1 ml/min (47% decrease) and filtration fraction significantly increased from 12.7 +/- 1.1 to 15.7 +/- 2.1% (24% increase) during glutamate infusion. Each of these variables returned to their pre-stimulus levels after ceasing the central stimulation. Fluid, sodium and potassium excretion were not changed by this stimulus. In conclusion, the results in this study suggest that a selective increase in sympathetic nerve activity to the kidney without change in renal perfusion pressure can cause constriction of the renal vasculature without alteration in sodium and water excretion.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-0010
DOI: 10.1097/00004872-200108000-00019
Abstract: To determine whether 6 weeks continuous treatment with an angiotensin converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo, since this treatment results in extensive phenotypic conversion of afferent arteriolar cells from contractile to endocrine-like, renin secretory cells. Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6 weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and renal blood flow were measured and renal responsiveness tested by constructing dose-response curves to bolus doses of phenylephrine, angiotensin II and acetylcholine delivered directly into the renal artery. ACE inhibition resulted in a significant shift to the left in the renal vascular conductance responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating enhanced, not reduced, responsiveness to these agents. There were no significant effects of chronic ACE inhibition on the conductance responses to phenylephrine. Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce renal vascular responsiveness to three vasoactive agents, suggesting that the phenotypic changes observed in the afferent arterioles and to a lesser extent the interlobular arteries, were either insignificant or compensated for by other changes in renal circulatory control.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1991
DOI: 10.1097/00005344-199117002-00006
Abstract: The lifier properties associated with the structural changes in the heart and resistance vessels in chronic hypertension together play a major role in maintaining the elevated blood pressure (BP) in chronic hypertension, which is greater than that of the initiating cause. In patients with primary hypertension, long-term antihypertensive drug therapy causes substantial regression of the structural changes, as assessed by normalization of the total peripheral resistance (including the nonautonomic component) and of the left ventricular (LV) mass. Reversal of LV hypertrophy (LVH) took considerably longer than reversal of the vascular changes and the more complete the reversal of LVH, the slower the rate of redevelopment of hypertension upon cessation of treatment. We observed no change in sympathetic activity or in renin-angiotensin-aldosterone levels during the redevelopment phase and we hypothesized that the cardiovascular lifiers played a role in pathogenesis. This hypothesis was examined in spontaneously hypertensive rats (SHRs), where the vascular lifier properties were developed substantially by 4 weeks of age, i.e., before the development of hypertension, whereas LVH occurred pari passu the rise in BP. When young SHRs were treated with enalapril for brief periods, there was almost complete long-term regression of vascular lifier properties, but attenuation of LVH and hypertension were both smaller and more transient. In 4-week-old SHRs, complete abolition of sympathetic activity had a minimal effect on vascular lifier properties, but affected LVH. Our findings suggest that LVH is as important in both the development and maintenance of hypertension as the structurally determined lifier properties of the resistance vessels.
Publisher: Wiley
Date: 07-2011
Publisher: AMPCo
Date: 04-2010
DOI: 10.5694/J.1326-5377.2010.TB03586.X
Abstract: Recent research has confirmed that Australian children and pregnant women are mildly iodine deficient. A considerable proportion of the pregnant population is moderately to severely iodine deficient. Even subclinical hypothyroidism in the mother, occurring as a consequence of iodine deficiency, can cause irreversible brain damage in the fetus, making it essential to avoid iodine deficiency in pregnancy. The proposal of Food Standards Australia and New Zealand (FSANZ) - Mandatory Iodine Fortification for Australia (P1003) - has been implemented. FSANZ openly admits P1003 is inadequate for covering the needs of pregnant women. Therefore, health professionals and the public must be properly informed about the limitations of this proposal. Views differ about the most effective measures to prevent iodine deficiency in Australia. We propose that women planning a pregnancy, and pregnant and lactating women should be advised to take an iodine supplement. Women with pre-existing thyroid disease should exercise caution and seek medical advice before taking a supplement.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1993
Abstract: We have previously shown that increasing the renal perfusion pressure by using an extracorporeal circuit in anesthetized rabbits resulted in a progressive fall in systemic arterial pressure. Prior ablation of the renal medulla with 2-bromoethylamine abolished the hypotensive response. In the present study, we investigated whether vasodilator prostanoids or platelet activating factor (PAF), both known to be produced in the renal medulla, were responsible for the hypotensive response to increased renal perfusion pressure. Anesthetized animals were treated with indomethacin (5 mg/kg + 0.5 mg/kg per hour), the PAF antagonist WEB 2086 (0.5 mg/kg + 0.5 mg/kg per hour), enalaprilat (2 mg/kg + 10 micrograms/kg per hour), or all three agents. In response to acute elevation of renal artery pressure to 170 mm Hg, systemic mean arterial pressure fell at 0.76 +/- 0.17, 0.59 +/- 0.08, and 0.76 +/- 0.17 mm Hg/min in the indomethacin, WEB 2086, and enalapril groups, respectively. These responses were not significantly different from the rate of 1.00 +/- 0.21 mm Hg/min in a control group that received vehicle infusion alone. Renal blood flow and the diuretic and natriuretic responses were also similar in all groups. Thus, increased renal perfusion pressure resulted in a progressive fall in systemic arterial pressure that was not mediated by PAF, prostaglandins, or suppression of renin release and angiotensin II production.
Publisher: Informa UK Limited
Date: 1997
DOI: 10.3109/08037059709086446
Abstract: Angiotensin II was infused at 0.5 ng/kg/min either directly into the left renal artery (n = 5) or intravenously (n = 4) for 28 days in conscious dogs. Renal artery infusion of angiotensin II had no significant effect on mean arterial pressure after 1 and 24 h, but pressure had increased by 12 +/- 2, 12 +/- 4, 8 +/- 3 and 13 +/- 3 mmHg on days 7, 14, 21 and 28, respectively, during infusion. Renal blood flow decreased significantly at 24 hours (p = 0.02) but was not significantly reduced subsequently. Over days 7-28, central venous pressure and haematocrit rose significantly but body weight did not change significantly. During intravenous infusion of angiotensin II, arterial pressure increased (5 +/- 4, 7 +/- 5 and 5 +/- 3 mmHg on days 7, 14 and 21, respectively), body weight rose and haematocrit fell significantly, but central venous pressure did not change. Thus, angiotensin II infused into the renal artery, at a dose which had no initial pressor effect, produced chronic, stable hypertension, with equivocal evidence of renal fluid retention. We conclude that elevated levels of angiotensin II in the kidney alone can cause chronic hypertension.
Publisher: Wiley
Date: 06-1982
DOI: 10.1111/J.1440-1681.1982.TB00804.X
Abstract: Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of acr transcription immediately after phage DNA injection and that Aca proteins subsequently repress this transcription. Without Aca activity, this strong transcription is lethal to a phage. Our results demonstrate how sufficient levels of Acr proteins accumulate early in the infection process to inhibit existing CRISPR-Cas complexes in the host cell. They also imply that the conserved role of Aca proteins is to mitigate the deleterious effects of strong constitutive transcription from acr promoters.
Publisher: Wiley
Date: 1997
DOI: 10.1111/J.1440-1681.1997.TB01784.X
Abstract: 1. In anaesthetized, fluid expanded rats rilmenidine has diuretic and natriuretic effects. There is strong evidence that the natriuresis is mediated by putative imidazoline receptors. In contrast, in conscious euvolaemic dogs rilmenidine has a diuretic effect that is entirely attributable to activation of alpha 2-adrenoceptors, but no natriuretic effect. To determine whether the effects of rilmenidine are truly species dependent, or merely dependent upon the influences of anaesthesia and volume status, we tested the effects of rilmenidine in pentobarbitone anaesthetized, volume-loaded dogs. 2. The effects of rilmenidine in anaesthetized, volume-loaded dogs were similar to those found in conscious euvolaemic dogs. Compared with vehicle treatment, levels of glomerular filtration rate, urine flow and haematocrit were increased following rilmenidine treatment. No effect of rilmenidine on sodium excretion was observed. 3. We conclude that the renal responses to rilmenidine in dogs are largely unaffected by anaesthesia and plasma volume status. In particular, the natriuretic effect seen in rats was not observed. We conclude that putative imidazoline receptors do not have a major influence on sodium excretion in dogs.
Publisher: American Physiological Society
Date: 12-1996
DOI: 10.1152/AJPREGU.1996.271.6.R1489
Abstract: Changes in renal sympathetic nerve activity (SNA) are postulated to influence renal function in selective ways, such that different levels of activation produce particular renal responses, initially in renin release, then sodium excretion, with changes in renal hemodynamics occurring only with much greater stimulus intensities. The aim of this study was to determine the renal hemodynamic and excretory responses to graded physiological increases in renal SNA induced by breathing different hypoxic gas mixtures. Experiments were performed in seven conscious rabbits subjected to four gas mixtures (14% O2, 10% O2, 10% O2 + 3% CO2, and 10% O2 + 5% CO2) and instrumented for recording of renal nerve activity. After a 30-min control period, rabbits were subjected to one of the four gas mixtures for 30 min, and then room air was resumed for a further 30 min. The four gas mixtures increased renal SNA by 14, 38, 49, and 165% respectively, but arterial pressure (thus renal perfusion pressure) was not altered by any of the gas mixtures. The greatest level of sympathetic activation produced significant falls in glomerular filtration rate (GFR), renal blood flow, sodium and fluid excretion, and significant increases in plasma renin activity. These returned to levels not significantly different from control conditions in the 30-min period after the gas mixture. When the changes to the various gas mixtures were analyzed within each rabbit, a significant linear relationship was found with all variables to the increase in SNA. Renal denervation in a separate group of seven rabbits completely abolished all of the above responses to the different gas mixtures. Thus graded activation of renal nerves induced by changes in inspired gas mixtures resulted in graded decreases in renal blood flow, GFR, and sodium excretion and graded increases in renin activity, with the changes occurring across a similar range of nerve activities there was no evidence for a selective change in any renal variable.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1994
DOI: 10.1097/00005344-199410000-00004
Abstract: We tested the effects and interactions of blockade of nitric oxide (NO) synthase and angiotensin-converting enzyme (ACE) on renal function. Six rabbits were studied four times, each at 14-day intervals. The treatments were intravenous (i.v.) vehicle, NG-nitro-L-arginine (L-NNA) 5 mg/kg, captopril 500 micrograms plus 3.3 micrograms/kg/min, or L-NNA plus captopril. The studies were performed in random order. Arterial blood pressure (BP), heart rate (HR), and clearance of H2O, Na+, Li+, [3H]inulin [glomerular filtration rate (GRF)], and paraaminohippuric acid (PAH, renal plasma flow) were measured for the hour before treatment and for 3 h after treatment. Renal blood flow (RBF), renal vascular conductance, and GFR were reduced by 36 +/- 4, 41 +/- 4, and 17 +/- 5%, respectively, after L-NNA treatment. Although captopril did not affect these variables significantly when given alone, it completely abolished the effects of L-NNA. After L-NNA administration, sodium excretion decreased by 41 +/- 11%, chiefly attributable to reduced GFR, although increased reabsorption of sodium also contributed. The site of this increased reabsorption was probably the proximal nephron, since Li+ reabsorption (a marker of proximal tubular sodium reabsorption) tended to increase by 8.4 +/- 4.8%. Captopril had a natriuretic effect chiefly attributable to reduced sodium reabsorption in the proximal nephron. When these agents were coadministered, proximal tubular sodium reabsorption did not change significantly. Our data suggest the existence of a functional interaction between ACE and NO synthase in control of RBF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 08-1980
DOI: 10.1113/JPHYSIOL.1980.SP013347
Abstract: 1. The effects of the state of renal vascular tone during induction of renal artery stenosis on the subsequent systemic blood pressure and renin responses have been studied in chronically instrumented, conscious dogs. 2. In one group of dogs, renal vascular tone was altered by brief (2-3 min) renal artery infusions of ACh, saline, methoxamine or angiotensin II during narrowing of the renal artery to reduce distal pressure to 40 mmHg. The infusions were turned off 1 min later. 3. The more vasoconstricted the kidney at the time of stenosis, the slower was the restoration of distal renal artery pressure and the greater the rises in systemic blood pressure, plasma renin activity (PRA) and effective stenosis resistance. At the end of 1 hr of stenosis, the rises in systemic blood pressure were 4.3 +/- 3.3, 11.3 +/- 3.3, 28.9 +/- 3.3 and 26.3 +/- 2.8 mmHg for the ACh, saline, methoxamine and angiotensin II-infused dogs respectively rises in PRA were 0.3 +/- 0.24, 1.18 +/- 0.42, 5.09 +/- 1.38 and 4.02 +/- 0.74 ng/ml. per hr respectively. 4. In another group of dogs a given aortic-renal artery pressure gradient was produced on two occasions: (i) with the animal conscious (ii) under brief sodium pentobarbitone anaesthesia and preparation for surgery. After 24 hr systemic blood pressure had risen by 15.7 +/- 3.6 mmHg above initial values when stenosis was induced under anaesthesia (P < 0.05) and only by 1.2 +/- 3.6 mmHg (N.S.) when it was induced with the animal conscious. Corresponding rises in PRA were 1.29 +/- 0.42 (P < 0.05) and 0.25 +/- 0.11 (N.S.) ng/ml. per hr. Establishment of a given gradient in the high vascular resistance kidney of the anaesthetized dog thus requires greater narrowing of the renal artery than in the lower resistance renal bed of the conscious animal. 5. The tone of the renal vascular bed is a major determinant of the severity of renal artery stenosis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2003
DOI: 10.1161/01.HYP.0000052949.85257.8E
Abstract: Preexisting chronic hypertension complicates up to 5% of pregnancies and is associated with an increased risk of low-birth-weight babies. Studies suggest that an adverse intrauterine environment leading to low birth weight is linked to an increased risk of cardiovascular disease, including hypertension, in the adult. In this study, the blood pressure of offspring from mothers with hypertension were followed up into adulthood. Two-kidney, 1-wrapped hypertension was induced in 7 female rabbits 5 other rabbits underwent sham surgery. Four weeks later, rabbits were mated, at which time mean arterial pressure was 118±3 and 87±5 mm Hg in the hypertensive and sham groups, respectively ( P .001). The blood pressure of 30-week-old females was 89±2 mm Hg in the offspring of hypertensive (n=14) and 79±1 mm Hg in the offspring of normotensive (n=13) mothers ( P .005). Also, plasma renin activity was significantly lower in the female offspring of hypertensive mothers at 10 weeks of age ( P .05), suggesting that development of the renin-angiotensin system was altered. In contrast, male offspring from hypertensive and normotensive mothers had similar mean arterial pressure and plasma renin activity. In conclusion, maternal secondary hypertension can “program” hypertension in female adult offspring. The results also suggest that there are gender-specific differences in sensitivity to altered in utero environmental influences.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2004
DOI: 10.1161/01.HYP.0000117140.52220.85
Abstract: This study investigated the effects of angiotensin II “slow pressor” hypertension on structure and function of nerves supplying the renal vasculature. Low-dose angiotensin II (10 ng/kg per minute, initially sub-pressor) or saline vehicle was infused intravenously for 21 days in rats, and the effects were compared in renal and mesenteric arteries. Mean arterial pressure averaged 12±2 mm Hg higher than in vehicle-infused rats at 21 days. Using electron microscopy, the innervation density of renal arcuate, but not mesenteric arteries of equivalent size, was significantly higher in angiotensin II-infused than in vehicle-infused rats. Functional testing on a pressure myograph revealed that constrictions evoked by nerve stimulation in arcuate arteries were 2.3±0.7-fold greater in vessels from angiotensin II-infused compared with vehicle-infused rats ( P .0001), whereas there was no significant difference in nerve-induced constrictions in mesenteric arteries. Sensitivity to and maximum litude of constrictions evoked by phenylephrine were not different in renal or mesenteric arteries between groups, suggesting that the increased neurally evoked constriction in renal arcuate arteries was not caused by postsynaptic changes. Endothelium-dependent vasorelaxation and the vessel wall physical properties were not different between the two groups in either artery. Thus, angiotensin II infusion appeared to evoke renal-specific increases in vessel innervation and increased vasoconstriction to nerve stimulation. These changes appear early and occur before changes in renal endothelial function are apparent. Thus, “slow pressor” angiotensin II hypertension is associated with increased renal innervation, compatible with a pathogenetic role.
Location: France
No related grants have been discovered for Warwick Peter Anderson.