ORCID Profile
0000-0003-4525-3565
Current Organisation
Universidade Federal de Minas Gerais
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Publisher: American Physiological Society
Date: 09-2008
DOI: 10.1152/AJPREGU.00181.2008
Abstract: Microinjection of the neuronal inhibitor muscimol into the dorsomedial hypothalamus (DMH) suppresses increases in heart rate (HR), mean arterial pressure (MAP), and circulating levels of adrenocorticotropic hormone (ACTH) evoked in air jet stress in conscious rats. Similar injection of muscimol into the caudal region of the lateral/dorsolateral periaqueductal gray (l/dlPAG) reduces autonomic responses evoked from the DMH, leading to the suggestion that neurons in the l/dlPAG may represent a descending relay for DMH-induced increases in HR and MAP. Here, we examined the role of neuronal activity in the caudal l/dlPAG on the increases in MAP, HR, and plasma ACTH seen in air jet stress in rats. Microinjection of muscimol into the caudal l/dlPAG reduced stress-induced increases in HR and MAP, while identical injections into sites just dorsal or into the rostral l/dlPAG had no effect. Microinjection of a combination of the glutamate receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) into the caudal l/dlPAG decreased stress-induced increases in HR alone only at the end of the 20-min stress period but significantly accelerated return to baseline. Surprisingly, microinjection of muscimol into the caudal l/dlPAG also reduced the stress-induced increase in plasma ACTH by 51%. Compared with unstressed control rats, rats exposed to air jet stress exhibited ∼3 times the number of Fos-positive neurons in the l/dlPAG. These findings suggest that neurons in the l/dlPAG are activated in air jet stress and that this activity contributes to increases in HR, MAP, and plasma ACTH.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.NEUROSCIENCE.2011.03.018
Abstract: Psychological stress elicits increases in sympathetic activity accompanied by a marked cardiovascular response. Revealing the relevant central mechanisms involved in this phenomenon could contribute significantly to our understanding of the pathogenesis of stress-related cardiovascular diseases, and the key to this understanding is the identification of the nuclei, pathways and neurotransmitters involved in the organization of the cardiovascular response to stress. The present review will focus specifically on the dorsomedial hypothalamus, a brain region now known to play a primary role in the synaptic integration underlying the cardiovascular response to emotional stress.
Publisher: Informa UK Limited
Date: 29-10-2014
DOI: 10.3109/00207454.2014.970256
Abstract: Resistance exercise (RE) is characterized to increase strength, tone, mass, and/or muscular endurance and also for produces many beneficial effects, such as blood pressure and osteoporosis reduction, diabetes mellitus control, and analgesia. However, few studies have investigated endogenous mechanisms involved in the RE-induced analgesia. Thus, the aim of this study was evaluate the role of the NO/CGMP/KATP pathway in the antinociception induced by RE. Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by mechanical nociceptive test (paw-withdrawal). To investigate the involvement of the NO/CGMP/KATP pathway the following nitric oxide synthase (NOS) non-specific and specific inhibitors were used: N-nitro-l-arginine (NOArg), Aminoguanidine, N5-(1-Iminoethyl)-l-ornithine dihydrocloride (l-NIO), Nω-Propyl-l-arginine (l-NPA) guanylyl cyclase inhibitor, 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) and KATP channel blocker, Glybenclamide all administered subcutaneously, intrathecally and intracerebroventricularly. Plasma and cerebrospinal fluid (CSF) nitrite levels were determined by spectrophotometry. The RE protocol produced antinociception, which was significantly reversed by NOS specific and unspecific inhibitors, guanylyl cyclase inhibitor (ODQ) and KATP channel blocker (Glybenclamide). RE was also responsible for increasing nitrite levels in both plasma and CSF. These finding suggest that the NO/CGMP/KATP pathway participates in antinociception induced by RE.
Publisher: American Physiological Society
Date: 15-04-2013
DOI: 10.1152/AJPREGU.00401.2012
Abstract: Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABA A antagonist bicuculline methiodide (BMI 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/d t), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/d t, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH L-DMH.
Publisher: Frontiers Media SA
Date: 04-06-2018
Publisher: Public Library of Science (PLoS)
Date: 14-11-2014
Publisher: American Physiological Society
Date: 10-2013
DOI: 10.1152/AJPHEART.00433.2013
Abstract: Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT 1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1–7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1–7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1–7) 61 ± 25 beats/min P 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1–7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1–7) [ΔHR: saline 100 ± 16 vs. ANG-(1–7) 18 ± 15 beats/min P 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also abolished after the treatment with ANG-(1–7) [ΔRSNA: saline 39% vs. ANG-(1–7) −23% P 0.05]. The tachycardia evoked by disinhibition of dorsomedial hypothalamus neurons, a key nucleus for the cardiovascular response to emotional stress, was reduced by ∼45% after intravenous injection of ANG-(1–7). In cardiomyocyte, the incubation with ANG-(1–7) (1 μM) markedly attenuated the increases in beating rate induced by isoproterenol. Our data show that activation of the ACE2/ANG-(1–7)/Mas axis attenuates stress-induced tachycardia. This effect might be either via the central nervous system reducing anxiety level and/or interfering with the positive chronotropy mediated by activation of cardiac β adrenergic receptors. Therefore, ANG-(1–7) might contribute to reduce the sympathetic load to the heart during situations of emotional stress, reducing the cardiovascular risk.
Publisher: Wiley
Date: 16-03-2016
Abstract: Cardiovascular (CV) representation has been identified within the insular cortex (IC) and a lateralization of function previously suggested. In order to further understand the role of IC on cardiovascular control, the present study compared the CV responses evoked by stimulation of N-metil-D-aspartate (NMDA) receptors in the right and left posterior IC at different rostrocaudal levels. Intracortical microinjections of NMDA were performed into the IC of male Wistar rats anaesthetized with urethane (1.4 g/kg) prepared for blood pressure, heart rate and renal sympathetic nerve activity. Gene expression of NMDA receptor subunits NR2A and NR2B in the IC was confirmed by RT-PCR. Immunofluorescence for the NMDA receptor NR1 subunit was demonstrated in the IC (coordinates anteroposterior (AP) +1.5, 0.0 and -1.5 mm). A cardiac sympathoinhibitory site was identified, more rostrally located than identified in previous studies. A site of sympathoexcitatory cardiac control was identified more caudal to this region in agreement with earlier work. Under the experimental conditions, no lateralization of cardiovascular function was identified with chemical stimulation eliciting the same responses from either left or right insular cortices. No tonic role of the insula on cardiovascular control was identified with the use of the NMDA antagonist, AP-5. Peri-insular microinjection of NMDA was without cardiovascular effect indicating the specificity of the insula as a cardiovascular regulatory site. The current study reveals a functional topography for autonomic cardiovascular control along the rostrocaudal axis of the posterior IC.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.BRAINRES.2012.02.021
Abstract: Previous evidence indicates that a balance between inhibitory gabaergic and excitatory angiotensinergic factors in the PVN is important for cardiovascular control. We investigated the cardiovascular response evoked from activation or blockade of GABA(A) receptors in the paraventricular nucleus (PVN), in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Brain Ang II and Ang-(1-7) levels were also determined. In functional experiments, TGR(ASrAOGEN) and Sprague-Dawley rats (SD, control) were anesthetized with urethane and blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. Brain Ang II and Ang-(1-7) levels were largely reduced in TGR(ASrAOGEN) compared with SD rats. Inhibition of PVN neurons with the GABA(A) agonist, muscimol (1 nmol/100 nL), resulted in an attenuated fall in all cardiovascular variables in TGR(ASrAOGEN) compared with SD rats. This difference was particularly pronounced in HR (TGR Mus -23±6 bpm vs. -77±9 bpm SD Mus P<0.05) and RSNA (TGR -3±10% vs.-29±8% SD P<0.05). Furthermore, the sympathetic response evoked by blockade of GABA(A) receptors in the PVN of TGR(ASrAOGEN) was also largely suppressed. The present data indicate that the sympathetic outflow mediated by PVN neurons under basal conditions is suppressed in TGR(ASrAOGEN) rats corroborating the functional significance of brain angiotensin production in the central regulation of sympathetic output to the cardiovascular system.
Publisher: Bentham Science Publishers Ltd.
Date: 31-05-2011
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.RESP.2015.10.012
Abstract: Threatening stimuli trigger rapid and coordinated behavioral responses supported by cardiorespiratory changes. The midbrain colliculi can generate coordinated orienting or defensive behavioral responses, and it has been proposed that collicular neurons also generate appropriate cardiovascular and respiratory responses to support such behaviors. We have shown previously that under conditions where collicular neurons are disinhibited, coordinated cardiovascular, somatomotor and respiratory responses can be evoked independently of the cortex by auditory, visual and somatosensory stimuli. Here we report that these natural stimuli effectively increase inspiratory time most likely though phase switching. As a result the pattern of phrenic and sympathetic coupling is an inspiratory-related sympathoexcitation. We propose that blockade of tonic GABAergic input in the midbrain colliculi permits alerting stimuli to drive command neurons that generate coordinated cardiovascular, respiratory and motor outputs. The outputs of these command neurons likely interact with the central respiratory pattern generator, however the precise output pathways mediating the coordinated autonomic and respiratory responses remain to be determined.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.NEULET.2012.06.021
Abstract: The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity.
Publisher: Wiley
Date: 09-07-2021
DOI: 10.1111/ENE.14987
Abstract: Damage to the insula results in cardiovascular complications. In rats, activation of N ‐methyl‐ d ‐aspartate receptors (NMDARs) in the intermediate region of the posterior insular cortex (iIC) results in sympathoexcitation, tachycardia and arterial pressure increases. Similarly, focal experimental hemorrhage at the iIC results in a marked sympathetic‐mediated increase in baseline heart rate. The dorsomedial hypothalamic region (DMH) is critical for the integration of sympathetic‐mediated tachycardic responses. Here, whether responses evoked from the iIC are dependent on a synaptic relay in the DMH was evaluated. Wistar rats were prepared for injections into the iIC and DMH. Anatomical (tracing combined with immunofluorescence) and functional experiments (cardiovascular and sympathetic recordings) were performed. The iIC sends dense projections to the DMH. Approximately 50% of iIC neurons projecting to the DMH express NMDARs, NR1 subunit. Blockade of glutamatergic receptors in the DMH abolishes the cardiovascular and autonomic responses evoked by the activation of NMDARs in the iIC (change in mean arterial pressure 7 ± 1 vs. 1 ± 1 mmHg after DMH blockade change in heart rate 28 ± 3 vs. 0 ± 3 bpm after DMH blockade change in renal sympathetic nerve activity 23% ± 1% vs. −1% ± 4% after DMH blockade). Experimental hemorrhage at the iIC resulted in a marked tachycardia (change 89 ± 14 bpm) that was attenuated by 65% ± 5% ( p = 0.0009) after glutamatergic blockade at the DMH. The iIC‐induced tachycardia is largely dependent upon a glutamatergic relay in the DMH. Our study reveals the presence of an excitatory glutamatergic pathway from the iIC to the DMH that may be involved in the cardiovascular alterations observed after insular stroke.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.BRAINRES.2014.01.043
Abstract: Maintenance of homeostasis in normal or stressful situations depends upon mechanisms controlling autonomic activity. Central requirement for changes in sympathetic output resulting from emotional stress must be adjusted to the input signals from visceral sensory afferent (feedback response) for an optimum cardiovascular performance. There is a large body of evidence indicating that emotional stress can lead to cardiovascular disease. Reviewing the descending pathways from dorsomedial hypothalamus, a key region involved in the cardiovascular response to emotional stress, we discuss the interactions between mechanisms controlling the sympathetic output to the cardiovascular system and the possible implications in cardiovascular disease.
Publisher: Informa UK Limited
Date: 04-03-2017
DOI: 10.1080/10253890.2017.1296949
Abstract: Angiotensin II (Ang II) acts as a pro-stress hormone, while other evidence indicates that angiotensin-(1-7) [Ang-(1-7)] attenuates physiological responses to emotional stress. To further test this hypothesis, in groups of 5-6 rats we evaluated autonomic, cardiovascular and behavioral parameters in male Sprague-Dawley (SD) and transgenic TGR(A1-7)3292 (TG) rats chronically overexpressing Ang-(1-7). Compared to SD rats, TG rats showed reduced baseline heart rate (HR SD 380 ± 16 versus TG 329 ± 9 beats per minute (bpm), mean ± standard error of mean, p < .05) and renal sympathetic discharge (SD 138 ± 4 versus TG 117 ± 5 spikes/second, p < .05). TG rats had an attenuated tachycardic response to acute air-puff stress (ΔHR: SD 51 ± 20 versus TG 1 ± 3 bpm p < .05), which was reversed by intracerebroventricular injection of the Mas receptor antagonist, A-779 (ΔHR: SD 51 ± 20 versus TG 63 ± 15 bpm). TG rats showed less anxious behavior on the elevated plus maze, as revealed by more entries into open arms (SD 2 ± 2 versus TG 47 ± 5% relative to total entries p < .05), and more time spent in the open arms (SD 5 ± 4 versus TG 53 ± 9% relative to total time, p < .05). By contrast with SD rats, diazepam (1.5 mg/kg, intraperitoneally) did not further reduce anxious behavior in TG rats, indicating a ceiling anxiolytic effect of Ang-(1-7) overexpression. Ang-(1-7) concentrations in hypothalamus and plasma, measured by mass spectrometry were two- and three-fold greater, respectively, in TG rats than in SD rats. Hence, increased endogenous Ang-(1-7) levels in TG rats diminishes renal sympathetic outflow and attenuates cardiac reactivity to emotional stress, which may be via central Mas receptors, and reduces anxious behavior. Lay summaryWe used a genetically modified rat model that produces above normal amounts of a peptide hormone called angiotensin-(1-7) to test whether this peptide can reduce some of the effects of stress. We found that angiotensin-(1-7), acting in the brain, can reduce anxiety and reduce the increase in heart rate associated with emotional stress. These findings may provide a lead for design of new drugs to reduce stress.
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.BRAINRES.2006.03.080
Abstract: Microinjection of the neuronal inhibitor muscimol into the midbrain lateral/dorsolateral periaqueductal gray (l/dlPAG) suppresses increases in heart rate (HR) and mean arterial pressure (MAP) evoked by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) into the dorsomedial hypothalamus (DMH) in rats. Injection of BMI into the DMH also increases body temperature (Tco) and motor activity. Here, our goal was to extend previous findings by examining the effect of microinjection of muscimol into the PAG on these thermogenic and behavioral responses in conscious freely moving rats. Microinjection of muscimol (300 pmol and 1 nmol) alone into the l/dlPAG reduced baseline Tco without affecting activity, HR, or MAP. Similar injection of a dose that failed to alter baseline Tco (100 pmol) suppressed the increases in Tco evoked from the DMH and significantly attenuated DMH-induced increases in locomotor activity. Whereas microinjection of 1 nmol muscimol into the ldlPAG abolished the increases in Tco evoked from the DMH and in fact lowered body temperature to a degree similar to that seen after this dose of muscimol alone, 1 nmol muscimol at adjacent sites outside the targeted region of the PAG had no significant effect on DMH-induced increases in Tco or any other parameter. These results indicate a role for neuronal activity in the l/dlPAG in (1) the temperature and behavioral responses to disinhibition of neurons in the DMH, and (2) the maintenance of basal body temperature in conscious freely moving rats.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.NEUROSCIENCE.2014.10.067
Abstract: Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats (2) changes in cardiovascular reactivity to air jet stress in conscious rats and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8% P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5% P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system.
Publisher: Wiley
Date: 27-02-2021
DOI: 10.1111/FCP.12648
Abstract: Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT – normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control ‐ CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air‐jet (10 L/min – restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR (ii) different stimuli evoked pressor and tachycardic responses (iii) CL and RI reduced pressor response to sound (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI (vi) air‐jet increased pressure and heart rate (vii) CL or RI attenuated the pressor responses to air‐jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air‐jet‐induced tachycardia.
Publisher: EDITORA SCIENTIFIC
Date: 2022
DOI: 10.47626/1516-4446-2021-2339
Abstract: Follow-up of patients affected by COVID-19 has unveiled remarkable findings. Among the several sequelae caused by SARS-CoV-2 viral infection, it is particularly noteworthy that patients are prone to developing depression, anxiety, cognitive disorders, and dementia as part of the post-COVID-19 syndrome. The multisystem aspects of this disease suggest that multiple mechanisms may converge towards post-infection clinical manifestations. The literature provides mechanistic hypotheses related to changes in classical neurotransmission evoked by SARS-CoV-2 infection nonetheless, the interaction of peripherally originated classical and non-canonic peptidergic systems may play a putative role in this neuropathology. A wealth of robust findings shows that hemoglobin-derived peptides are able to control cognition, memory, anxiety, and depression through different mechanisms. Early erythrocytic death is found during COVID-19, which would cause excess production of hemoglobin-derived peptides. Following from this premise, the present review sheds light on a possible involvement of hemoglobin-derived molecules in the COVID-19 pathophysiology by fostering neuroscientific evidence that supports the contribution of this non-canonic peptidergic pathway. This rationale may broaden knowledge beyond the currently available data, motivating further studies in the field and paving ways for novel laboratory tests and clinical approaches.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.AUTNEU.2011.03.006
Abstract: In this study we assessed the role of Bezold-Jarisch reflex (BJR) in the regulation of blood pressure (BP) of malnourished (MN) and control rats (CN) with sino-aortic denervation (SAD). Fischer rats were fed diets containing either 6% (MN) or 15% (CN) protein for 35 days after weaning. These rats underwent sham or SAD and catheterization of femoral artery and vein for BP measurements and drug injection. Phenylbiguanide (PBG 5 μg/kg, i.v.) for activation BJR, produced bradycardia (-317±22 bpm for CN vs. -372±16 bpm for MN) and hypotension (-57±4 mm Hg for CN vs. -54±6 mm Hg for MN. After SAD, MN rats had reduced hypotensive (-37±7 mm Hg for MN vs. -82±6 mm Hg for CN) and bradycardic (-124±17 for MN vs. -414±20 bpm CN) responses to BJR activation. To evaluate the contribution of the parasympathetic component due to BJR for the fall in BP, methyl atropine bromide, was given between two injections of PBG (5 μg/kg) separated by 10 min each other. Both bradycardic (-216±21 bpm before and -4±3 bpm after for CN -226±43 bpm before and -9±20 bpm after for MN) and hypotensive (-42±4 mm Hg before and -6±1 mm Hg after for CN -33±9 mm Hg before and -5±2 mm Hg after for MN) responses were abolished in CN and MN groups. These data indicate that dietary protein malnutrition changes the relation between baroreflex and BJR required for maintenance of the BP during malnourishment.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.AUTNEU.2017.01.001
Abstract: The autonomic response to emotional stress, while involving several target organs, includes an important increase in sympathetic drive to the heart. There is le evidence that cardiac sympathetic innervation is lateralized, and asymmetric autonomic output to the heart during stress is postulated to be a causal factor that precipitates cardiac arrhythmias. Recent animal studies provided a new picture of the central pathways involved in the cardiac sympathetic response evoked by emotional stress, pointing out a key role for the region of dorsomedial hypothalamus. However, how much of this information can be extrapolated to humans? Analysis of human functional imaging data at rest or during emotional stress shows some consistency with the components that integrate these pathways, and attention must be given to the asymmetric activation of subcortical sites. In this short review, we will discuss related findings in humans and animals, aiming to understand the neurogenic background for the origin of emotional stress-induced cardiac arrhythmias.
Publisher: American Physiological Society
Date: 15-09-2015
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.NEUROSCIENCE.2006.08.062
Abstract: The rostral ventrolateral medulla (RVLM) has been proposed as a region playing a major role in the tonic and reflex control of sympathetic vasomotor activity and blood pressure. Pharmacological activation of GABA(A) receptors with muscimol in the RVLM of anesthetized rats results in a large fall in mean arterial pressure (MAP), heart rate (HR) and sympathetic activity. In this study we evaluated the effects of activation of GABA receptors in the RVLM of conscious, freely moving rats. Bilateral microinjections of muscimol into the RVLM of conscious rats produced a large fall in MAP (-38+/-4 mm Hg, n=7) when compared with saline injections (NaCl 0.9%, 7+/-1 mm Hg, n=4). The decrease in MAP evoked by muscimol was accompanied by a significant increase in HR (muscimol 69+/-13 bpm vs. vehicle -33+/-12 bpm, P<0.05), an effect that was completely abolished by beta1 adrenergic receptor blockade. Conversely, bilateral microinjections of GABA(B) agonist, baclofen, evoked a pressor response, but in this case, the increase was not significantly different from that evoked by vehicle injections. These results 1) indicate that GABA(A) receptors have a powerful influence on the resting activity of RVLM neurons in conscious rats 2) indicate that a compensatory sympathetic-mediated tachycardia is present after inhibition of RVLM neurons in conscious rats 3) confirm and extend previous findings showing that RVLM neurons are critical for blood pressure maintenance even in normal non-anesthetized conditions.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0006-8993(03)03157-3
Abstract: Activation of neurons in the region of the dorsomedial hypothalamus (DMH), by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) results in increases in arterial pressure, heart rate as well as behavioral changes similar to those evoked by acute emotional stress. Previous anatomic studies clearly demonstrated projections from the DMH to the midbrain periaqueductal gray (PAG), a brain region implicated in the organization of behavioral strategies associated with specific cardiovascular responses. In this study, physiological experiments in conscious rats were used to investigate the functional significance of this pathway. Unilateral inhibition of the lateral dorsolateral region of the PAG (l/dlPAG) with the GABA(A) receptor agonist, muscimol (1 nmol/100 nl) largely reduced the tachycardia and the pressor response produced by microinjection of BMI (10 pmol/100 nl) into the ipsilateral DMH. In contrast, inhibition of the ventrolateral PAG (vlPAG) region had no significant effect on the cardiovascular response evoked from disinhibition of the ipsilateral DMH. Our present results indicate that the l/dlPAG region is an important synaptic relay in the descending cardiovascular pathways from the DMH.
Publisher: Wiley
Date: 13-03-2009
Publisher: Elsevier BV
Date: 09-2020
Publisher: American Physiological Society
Date: 15-10-2014
DOI: 10.1152/AJPREGU.00165.2014
Abstract: The midbrain superior and inferior colliculi have critical roles in generating coordinated orienting or defensive behavioral responses to environmental stimuli, and it has been proposed that neurons within the colliculi can also generate appropriate cardiovascular and respiratory responses to support such behavioral responses. We have previously shown that activation of neurons within a circumscribed region in the deep layers of the superior colliculus and in the central and external nuclei of the inferior colliculus can evoke a response characterized by intense and highly synchronized bursts of renal sympathetic nerve activity and phrenic nerve activity. In this study, we tested the hypothesis that, under conditions in which collicular neurons are disinhibited, coordinated cardiovascular, somatomotor, and respiratory responses can be evoked by natural environmental stimuli. In response to natural auditory, visual, or somatosensory stimuli, powerful synchronized increases in sympathetic, respiratory, and somatomotor activity were generated following blockade of GABA A receptors in a specific region in the midbrain colliculi of anesthetized rats, but not under control conditions. Such responses still occurred after removal of most of the forebrain, including the amygdala and hypothalamus, indicating that the essential pathways mediating these coordinated responses were located within the brain stem. The temporal relationships between the different outputs suggest that they are driven by a common population of “command neurons” within the colliculi.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.BRAINRES.2014.11.006
Abstract: The basolateral amygdala (BLA) plays a critical role in mediating physiological responses to emotional stress. Recent data suggest that angiotensin-(1-7) [Ang-(1-7)] can act centrally attenuating the cardiovascular response to acute stress. We investigated whether Ang-(1-7) in the BLA plays a role in the cardiovascular response to emotional stress. Under anesthesia, guide cannulas were implanted into the BLA of Wistar rats. Five days later, the femoral artery was cannulated for mean arterial pressure (MAP) and heart rate (HR) recordings. Microinjections of Ang-(1-7) (5 or 50 pmol), the Mas receptor antagonist A-779 (100 pmol), Ang-(1-7)+A-779 (50 + 100 pmol, respectively), or vehicle (NaCl 0.9%, control) were performed after 24h and rats were then submitted to stress trials. Injection of Ang-(1-7) into the BLA blocked the tachycardia (ΔHR: vehicle 135 ± 23 vs. Ang-(1-7) 9 ± 12 bpm P<0.05) and the pressor response (ΔMAP: vehicle 28 ± 3 mmHg vs. Ang-(1-7) 6 ± 2 mmHg P<0.05) produced by air jet stress. These effects were completely reversed by A-779 (ΔHR: 109 ± 11 bpm ΔMAP: 18 ± 2 mmHg). Ang-(1-7) into the BLA also attenuated the pressor response evoked by cage-switch stress paradigm. These findings indicate that Ang-(1-7) can act in the BLA through the Mas receptors modulating the cardiovascular response evoked by emotional stress.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.NEUROSCIENCE.2009.09.018
Abstract: Neurons in the dorsomedial hypothalamus (DMH) play a key role in mediating tachycardia elicited by emotional stress. DMH activation by microinjections of the GABA(A) antagonist evokes tachycardia and physiological changes typically seen in experimental stress. DMH inhibition abolishes the tachycardia evoked by stress. Based on anatomic evidences for lateralization in the pathways from DMH, we investigated a possible inter-hemispheric difference in DMH-evoked cardiovascular responses. In anesthetized rats we compared changes in heart rate (HR), renal sympathetic activity (RSNA), mesenteric blood flow (MBF) and tail vascular conductance produced by activation of right (R) and left (L) sides of the DMH. We also evaluated the tachycardia produced by air jet stress after inhibition of R or L DMH. There were always greater increases in RSNA when bicuculline was injected ipsilaterally to the side where these parameters were recorded (average DeltaRSNA: L=+50% and R=+26% P<0.05). Compared to pre-injection values, right DMH activation caused pronounced decrease (0.87+/-0.1% vs. 0.4+/-0.11%/mm Hg P<0.05), whereas bicuculline methiodide (BMI) into left DMH produced no significant changes (0.95+/-0.09% vs. 1.04+/-0.25%/mm Hg) in tail vascular conductance. R or L DMH disinhibition produced decreases in MBF, but no differences in the range of these changes were observed. Activation of the right DMH caused greater tachycardia compared to the left DMH activation (average DeltaHR: R=+92 bpm L=+48 bpm P<0.05). Tachycardia evoked by air jet stress was smallest after right DMH inhibition (average DeltaHR: R=+57 bpm and L=+134 bpm P<0.05). These results indicate that the descending cardiovascular pathways from DMH are predominantly lateralized and the right DMH might exert a prominent control on heart rate changes during emotional stress.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.LFS.2018.01.019
Abstract: Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the litude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin lified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.
Publisher: American Physiological Society
Date: 10-2004
DOI: 10.1152/AJPREGU.00221.2004
Abstract: The dorsomedial hypothalamic nucleus (DMH) is believed to play a key role in mediating vasomotor and cardiac responses evoked by an acute stress. Inhibition of neurons in the rostral ventrolateral medulla (RVLM) greatly reduces the increase in renal sympathetic nerve activity (RSNA) evoked by activation of the DMH, indicating that RVLM neurons mediate, at least in part, the vasomotor component of the DMH-evoked response. In this study, the first aim was to determine whether neurons in the medullary raphe pallidus (RP) region also contribute to the DMH-evoked vasomotor response, because it has been shown that the DMH-evoked tachycardia is mediated by the RP region. The second aim was to directly assess the effect of DMH activation on the firing rate of RVLM sympathetic premotor neurons. In urethane-anesthetized rats, injection of the GABA A receptor agonist muscimol (but not vehicle solution) in the RP region caused a modest (∼25%) but significant reduction in the increase in RSNA evoked by DMH disinhibition (by microinjection of bicuculline). In other experiments, disinhibition of the DMH resulted in a powerful excitation (increase in firing rate of ∼400%) of 5 out of 6 spinally projecting barosensitive neurons in the RVLM. The results indicate that neurons in the RP region make a modest contribution to the renal sympathoexcitatory response evoked from the DMH and also that sympathetic premotor neurons in the RVLM receive strong excitatory inputs from DMH neurons, consistent with the view that the RVLM plays a key role in mediating sympathetic vasomotor responses arising from the DMH.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.NEULET.2010.11.014
Abstract: Malnutrition affects cardiovascular reflexes, including chemoreflex and baroreflex. In this study we assessed the hypothesis that malnourishment changes the responses in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) evoked from Bezold-Jarisch reflex (BJR). Fischer rats were fed diets containing either (6% malnourished or 14% control) protein for 35 days after weaning. There were no differences in baseline MAP (102 ± 4 vs. 95 ± 3 mmHg) whereas higher baseline HR (478 ± 18 vs. 360 ± 11 bpm P<0.05,) and reduced sympathoinhibition (ΔRSNA=-54 ± 9 vs. -84 ± 7% P=0.0208) to BJR activation were found in malnourished rats. We conclude that malnutrition affects the sympathetic control of BJR.
Publisher: Informa UK Limited
Date: 22-05-2018
Publisher: American Physiological Society
Date: 15-01-2015
Publisher: American Physiological Society
Date: 12-2010
Publisher: Elsevier BV
Date: 11-2020
Publisher: FapUNIFESP (SciELO)
Date: 06-2000
DOI: 10.1590/S0100-879X2000000600005
Abstract: Neurons in the rostral and caudal parts of the ventrolateral medulla (VLM) play a pivotal role in the regulation of sympathetic vasomotor activity and blood pressure. Studies in several species, including humans, have shown that these regions contain a high density of AT1 receptors specifically associated with neurons that regulate the sympathetic vasomotor outflow, or the secretion of vasopressin from the hypothalamus. It is well established that specific activation of AT1 receptors by application of exogenous angiotensin II in the rostral and caudal VLM excites sympathoexcitatory and sympathoinhibitory neurons, respectively, but the physiological role of these receptors in the normal synaptic regulation of VLM neurons is not known. In this paper we review studies which have defined the effects of specific activation or blockade of these receptors on cardiovascular function, and discuss what these findings tell us with regard to the physiological role of AT1 receptors in the VLM in the tonic and phasic regulation of sympathetic vasomotor activity and blood pressure.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.NEUROSCIENCE.2005.12.041
Abstract: Neurons in the region of dorsomedial hypothalamus are involved in the organization of the physiological responses to emotional stress. We have recently shown that the cardiovascular response evoked by activation of dorsomedial hypothalamus neurons is largely dependent on a synaptic relay with the lateral/dorsolateral periaqueductal gray region. In this study, we aimed to investigate whether excitatory amino acid receptors at the lateral/dorsolateral periaqueductal gray region are involved in mediating the response evoked by activation of dorsomedial hypothalamus neurons. In conscious rats, the cardiovascular effects produced by microinjection of GABA(A) receptor antagonist, bicuculline methiodide into the dorsomedial hypothalamus were evaluated before and after injection of different excitatory amino acid antagonists into lateral/dorsolateral periaqueductal gray region. Pretreatment of lateral/dorsolateral periaqueductal gray region with the non-selective ionotropic excitatory amino acid receptor antagonist kynurenic acid or with the N-methyl-D-aspartate receptor-selective antagonist, MK-801, largely reduced the tachycardic and pressor effects evoked by activation of dorsomedial hypothalamus neurons by bicuculline methiodide microinjection (heart rate 90 and 74% blood pressure 81 and 84%, respectively). The non-N-methyl-D-aspartate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, did not alter the cardiovascular response evoked by dorsomedial hypothalamus activation. In an additional series of experiments, microinjection of the N-methyl-D-aspartate receptor agonist, N-methyl-D-aspartate, into the lateral/dorsolateral periaqueductal gray region, evoked an increase in heart rate and a pressor response that was accompanied by an increase in locomotor activity. These effects were not altered by pretreatment of lateral/dorsolateral periaqueductal gray region neurons with 6-cyano-7-nitroquinoxaline-2,3-dione but were completely abolished by MK-801. Altogether, these findings indicate that the cardiovascular response evoked by dorsomedial hypothalamus activation involves a synaptic relay at the lateral/dorsolateral periaqueductal gray region that is mediated at least in large part by excitatory amino acid receptors, possibly N-methyl-D-aspartate receptors.
No related grants have been discovered for Marco Antonio Peliky Fontes.