ORCID Profile
0000-0003-2471-5935
Current Organisation
La Trobe University - Bendigo Campus
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Publisher: Informa UK Limited
Date: 1997
DOI: 10.3109/10641969709083195
Abstract: This study examined the possible contribution of the brain renin-angiotensin system on the sympathetic activation induced by hypoxia in conscious rabbits. Blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after fourth ventricular administration of either losartan (10 micrograms in 25 microliters), enalaprilat (500 ng in 25 microliters) or Ringer's (25 microliters). Hypoxia increased the RSNA by 113% and slightly decreased HR without changing BP. It also increased the variability of BP or HR in the 0.2-0.4 Hz frequency domain. Losartan and enalaprilat did not change the resting BP or HR but elevated the RSNA increase seen during hypoxia. Our results suggest that central angiotensin is involved in mediating response to chemoreceptor activation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1993
Publisher: Wiley
Date: 12-1997
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0165-1838(98)00105-2
Abstract: In 10 conscious rabbits, the baroreceptor-heart rate (HR) reflex effects of centrally acting antihypertensive agents with high affinity for imidazoline receptors (IRs), moxonidine and rilmenidine, were compared with clonidine which acts predominantly via central alpha2-adrenoceptors. Dose regimens were chosen to give similar hypotension (-17+/-1 mm Hg) and bradycardia (-27+/-2 b/min) for all three agents given into the fourth ventricle. Baroreceptor-HR reflex curves were assessed by i.v. drug induced changes in blood pressure. With all treatments, the baroreflex curves with both vagal and sympathetic effectors intact were shifted to the left, corresponding to the hypotension, and the bradycardia plateau was reduced. Rilmenidine and moxonidine also reduced the upper plateau such that the curves were shifted parallel down the HR scale with no change in the HR range. By contrast, clonidine only decreased the lower plateau, and thus increased HR range (+19+/-6%). Moxonidine, but not rilmenidine, reduced the baroreflex gain by reducing the curvature. Clonidine also decreased curvature but this did not result in a reduction in gain as it was offset by the increase in HR range. The gain and range of the cardiac sympathetic component, as assessed after vagal blockade, was reduced by rilmenidine by 53 and 40% respectively, but was not affected by the other agents. The calculated vagal component of the curves showed that all agents produced a greater vagal bradycardia in response to a rise in pressure and that both rilmenidine and clonidine increased vagal HR range. The present study results show that many of the baroreflex effects of clonidine, such as facilitating cardiac vagal responses, are shared by the second generation agent rilmenidine, suggesting that they are primarily due to alpha2-adrenoceptor activation. In addition, the inhibition of the sympathetic component of the baroreflex, observed with rilmenidine, and not clonidine suggests that this effect may involve IRs. By contrast moxonidine, the most specific agent for I1 receptors, produces mainly a baroreflex independent inhibition of cardiac sympathetic activity with little effect on vagal activity.
Publisher: Elsevier BV
Date: 1997
DOI: 10.1016/S0197-0186(96)00044-7
Abstract: Agmatine, an endogenous clonidine-displacing substance, has been shown to have an affinity for both alpha 2-adrenoceptors and imidazoline receptors (IR). In conscious rabbits, we have examined the cardiovascular effects of agmatine and its interaction with clonidine, a presumed agonist and 2-methoxyidazoxan, an antagonist at alpha 2-adrenoceptors. We have also examined the effect of agmatine on agents having high affinity for I1-imidazoline receptors namely moxonidine (agonist) and efaroxan (antagonist). Initial dose-response studies showed that agmatine administered in low doses (0.01-10 micrograms/kg) into the fourth ventricle did not change mean arterial pressure but did produce a dose-dependent bradycardia (maximum -16 +/- 3 beats/min). A higher dose of 100 micrograms/kg produced an adverse reaction in the conscious animals accompanied by a marked increase in mean arterial pressure and a reversal of the bradycardia. This is in contrast to the effects of fourth ventricular clonidine and moxonidine, which caused a dose-dependent fall in both mean arterial pressure and heart rate. Agmatine when administered at the highest well-tolerated dose of 10 micrograms/kg did not further alter the clonidine-induced hypotension but produced a greater bradycardia (-12 +/- 4 beats/min clonidine -29 +/- 4 beats/min clonidine plus agmatine p < 0.05). Similarly, the hypotension induced by moxonidine was not altered by agmatine but heart rate was reduced after the addition of agmatine (p < 0.01). Efaroxan and 2-methoxy-idazoxan, at doses which produced no effects when given alone, similarly reversed the fall in heart rate elicited by agmatine and caused a small but significant rise in mean arterial pressure. We have previously shown that the doses of these antagonists used in this study produce an equal reversal of the bradycardia induced by fourth ventricular alpha-methyldopa (alpha 2-adrenoceptor agonist) and clonidine and hence have similar alpha 2-adrenoceptor blocking effects. Our results show that agmatine produces bradycardia as does moxonidine and clonidine but does not mimic or block the hypotensive responses to these agents. These findings do not support the hypothesis that agmatine is an endogenous ligand for IR. However, the bradycardia induced by agmatine may be mediated via alpha 2-adrenoceptors since it was equally blocked by efaroxan and 2-methoxy-idazoxan. Thus while alpha 2-adrenoceptor actions of agmatine on heart rate are evident at relatively low doses, the reason for the lack of alpha 2-adrenoceptor mediated hypotension is not known.
Publisher: American Physiological Society
Date: 10-1998
DOI: 10.1152/AJPREGU.1998.275.4.R1174
Abstract: In the present study, we examined the effect of blockade of the brain stem renin-angiotensin system on renal sympathetic baroreflexes and chemoreflexes in conscious rabbits and examined the role of central catecholaminergic pathways in these responses. Eleven rabbits underwent preliminary surgical instrumentation and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 μg/kg) or ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O 2 + 3% CO 2 ) before and after central administration of either Ringer solution, the ANG II receptor antagonist losartan (10 μg), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and enalaprilat increased the RSNA upper plateau in intact rabbits but had no effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex curves were observed. Thus the effect of losartan to increase RSNA, particularly during hypoxia and baroreceptor unloading, being abolished by central noradrenergic depletion suggests that the endogenous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergic pathways.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2003
DOI: 10.1097/00004872-200301000-00027
Abstract: To determine the involvement of central imidazoline receptors in the cardiovascular actions of the chronically administered antihypertensive agents moxonidine, rilmenidine and clonidine. In 21 rabbits with implanted fourth-ventricular catheters, we investigated the central effects of three cumulative doses of an I(1)-imidazoline/alpha(2)-adrenoceptor antagonist, efaroxan, and of an alpha(2)-adrenoceptor antagonist, 2-methoxyidazoxan (2-MI), on the changes in blood pressure and heart rate (HR) elicited by chronic subcutaneous administration of moxonidine, rilmenidine and clonidine, after 1 and 3 weeks of treatment. A low, medium and high dose of 2-MI was matched to three doses of efaroxan, such that each produced equal reversal of the hypotension induced by fourth-ventricular alpha-methyldopa and hence produced a similar degree of alpha(2)-adrenoceptor blockade. Clonidine and moxonidine, at doses of 1 mg/kg per day, and rilmenidine at 5 mg/kg per day, produced sustained reductions in mean arterial pressure of 13 +/- 3, 15 +/- 2 and 13 +/- 2 mmHg, respectively over the 3-week treatment period, but did not alter HR. Central administration of efaroxan on day 9 and day 23 of treatment produced a greater increase in blood pressure than did 2-MI with all three antihypertensive agents. Blood pressure reached levels that were significantly above the original control values. By contrast, the alpha(2)-adrenoceptor antagonist 2-MI only induced a rebound blood pressure effect in clonidine- and to a lesser extent in rilmenidine-treated rabbits. Both efaroxan and 2-MI produced a similar degree of tachycardia in moxonidine-, rilmenidine- and clonidine-treated animals.(2) The greater effect of efaroxan compared to the alpha(2)-adrenoceptor antagonist 2-MI suggests that the hypotension induced by chronic subcutaneous administration of moxonidine, rilmenidine and clonidine is mediated predominantly via an action on central imidazoline receptors. Furthermore, all agents showed a propensity to produce rebound hypertension with imidazoline receptor blockade. However, only clonidine showed a rebound phenomenon when challenged by acute central alpha(2)-adrenoceptor blockade
Publisher: American Physiological Society
Date: 02-2000
DOI: 10.1152/AJPHEART.2000.278.2.H558
Abstract: The effect of chronic activation or inhibition of central ANG II receptors on cardiac baroreflex function in conscious normotensive rabbits was examined. Animals received a fourth ventricular (4V) infusion of ANG II (30 and 100 ng/h), losartan (3 and 30 μg/h), or Ringer solution (2 μl/h) for 2 wk. After 1 and 2 wk, ANG II (100 ng/h) decreased cardiac baroreflex gain by 20 and 37%, respectively ( P = 0.015), whereas losartan (30 μg/h) increased baroreflex gain by 24 and 58%, respectively ( P = 0.02). Within 1 wk of the end of the infusions, cardiac baroreflex gain had returned to control. Ringer solution or the lower doses of ANG II or losartan did not modify the cardiac baroreflex function. Blood pressure and heart rate were not altered by any treatment, nor was their variability affected. These data demonstrate a novel long-term modulation of cardiac baroreflexes by endogenous ANG II that is independent of blood pressure level.
Publisher: Elsevier BV
Date: 09-1996
Abstract: Short-term (one week) and chronic (six week) cardiovascular effects of orally administered perindopril were examined in the rabbit to demonstrate if short-term results can predict chronic outcomes. In short-term treatment, five doses of perindopril were examined in random order separated by a one week recovery period in each of six rabbits. Two doses of perindopril which resulted in a moderate hypotensive effect (-14 mmHg) and no hypotensive effect, respectively, were then selected for long-term treatment. Each rabbit in the short-term study received perindopril in doses of 0.01, 0.06, 0.32, 1.8 and 10 mg kg-1 day-1 for a week at a time. Rabbits on long-term treatment received either 0.3 or 0.01 mg kg-1 day-1 perindopril for six weeks. All rabbits had their mean arterial blood pressure (MAP) and heart rate recorded throughout treatment. Plasma angiotensin I (AngI), perindoprilat, angiotensin converting enzyme (ACE) inhibition were also assayed. Perindopril treatment for one week produced a dose-dependent hypotensive effect with the threshold dose, 0.06 mg kg-1 day-1, producing a 6.5 +/- 1.8 mmHg fall in MAP. The highest dose (10.0 mg kg-1 day-1) produced a large fall in blood pressure of -29.6 +/- 4.2 mmHg. The 0.01 and 0.06 mg kg-1 day-1 doses of perindopril produced an average 2.65 fold increase in plasma AngI levels compared to the initial control. The three higher doses (0.32-10.0 mg kg-1 day-1) of perindopril produced an equivalent 5.7 fold increase in plasma AngI levels compared to the initial controls. However, over six weeks 0.01 mg kg-1 day-1 perindopril induced a similar decrease in MAP as the 30 fold higher dose (-9.3 mmHg compared to -11.7 mmHg,). This was in spite of a 3 fold difference in plasma perindoprilat concentrations between the high and low dose perindopril groups. Plasma ACE inhibition was > 80% with both doses of perindopril. The results indicate that while perindopril decreases MAP in a dose-dependent manner in short-term (one week) periods, over longer treatment times (six weeks) low concentrations of perindopril, non-hypotensive with short-term treatment, may be as anti-hypertensive as considerably higher doses.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1996
Abstract: Abstract Previous studies have shown that angiotensin II (Ang II) can activate cardiovascular neurons within the medulla oblongata via an action on specific receptors. The purpose of this study was to determine the distribution of neurons within the medulla activated by infusion of Ang II into the fourth ventricle of conscious rabbits, using the expression of Fos, the protein product of the immediate early gene c- fos as a marker of neuronal activation. Experiments were done in both intact and barodenervated animals. In comparison with a control group infused with Ringer’s solution alone, in both intact and barodenervated animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a significant increase in the number of Fos-positive neurons in the nucleus of the solitary tract and in the rostral, intermediate, and caudal parts of the ventrolateral medulla. Double-labeling for Fos and tyrosine hydroxylase immunoreactivity showed that 50% to 75% of Fos-positive cells in the rostral, intermediate, and caudal ventrolateral medulla and 30% to 40% of Fos-positive cells in the nucleus of the solitary tract were also positive for tyrosine hydroxylase in both intact and barodenervated animals. The distribution of Fos-positive neurons corresponded very closely to the location of Ang II receptor binding sites as previously determined in the rabbit. The results indicate that medullary neurons activated by Ang II are located in discrete regions within the nucleus of the solitary tract and ventrolateral medulla and include, in all of these regions, both catecholamine and noncatecholamine neurons.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2021
DOI: 10.1186/S13047-021-00466-8
Abstract: Developing since colonisation, Australia’s healthcare system has dismissed an ongoing and successful First Nations health paradigm in place for 60,000 years. From Captain James Cook documenting ‘very old’ First Nations Peoples being ‘far more happier than we Europeans’ and Governor Arthur Phillip naming Manly in admiration of the physical health of Gadigal men of the Eora Nation, to anthropologist Daisy Bates’ observation of First Nations Peoples living ‘into their eighties’ and having a higher life expectancy than Europeans our healthcare system’s shameful cultural safety deficit has allowed for an Aboriginal and Torres Strait Islander child born in Australia today to expect to live 9 years less than a non-Indigenous child. Disproportionately negative healthcare outcomes including early onset diabetes-related foot disease and high rates of lower limb utation in Aboriginal and Torres Strait Islander Peoples contribute to this gross inequity. In 2020, the Australian Health Practitioner Regulation Authority released the National Scheme’s Aboriginal and Torres Strait Islander Health and Cultural Safety Strategy 2020–2025 - empowering all registered health practitioners within Australia to provide health care to Aboriginal and Torres Strait Islander Peoples that is inclusive, respectful and safe, as judged by the recipient of care. This recently released strategy is critically important to the podiatry profession in Australia. As clinicians, researchers and educators we have a collective responsibility to engage with this strategy of cultural safety. This commentary defines cultural safety for podiatry and outlines the components of the strategy in the context of our profession. Discussion considers the impact of the strategy on podiatry. It identifies mechanisms for podiatrists in all settings to facilitate safer practice, thereby advancing healthcare to produce more equitable outcomes. Aboriginal and Torres Strait Islander Peoples access health services more frequently and have better health outcomes where provision of care is culturally safe. By engaging with the National Scheme’s Aboriginal and Torres Strait Islander Health and Cultural Safety Strategy, all registered podiatrists in Australia can contribute to achieving equity in health outcomes for Aboriginal and Torres Strait Islander Peoples.
Publisher: SAGE Publications
Date: 04-2023
DOI: 10.1177/21582440231163834
Abstract: The inclusion of First Nations health curricula in programs is critical for the development of culturally safe graduates, however, less is known about how to embed content into curriculum in ways that reflect best practice and pedagogy. The aim of this scoping review was to describe methods and processes of First Nations health curriculum development in nursing, medical, dentistry, and allied health entry-level programs in international peer-reviewed journals. Systematic searches of databases were completed including CINAHL, Proquest, Medline, and Informit with additional searches in Google Scholar and First Nations-led journals. A total of 104 articles met inclusion criteria the majority relating to medicine ( n = 38) and nursing/midwifery ( n = 17) student cohorts. Methods and processes for embedding First Nations health content are described, including First Nations-led development and co-leadership, resulting in a suggested model for curriculum development. Evidence-informed curriculum development is critical to ensure effective methods and processes are adopted and cultural safety learning outcomes are achieved.
Publisher: Elsevier BV
Date: 02-2022
Location: Australia
No related grants have been discovered for Shirley Godwin.