Importance of angiotensinergic mechanisms for the pressor response to L-glutamate into the rostral ventrolateral medulla

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Kidney-Induced Hypertension Depends on Superoxide Signaling in the Rostral Ventrolateral Medulla

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Swimming Exercise Changes Hemodynamic Responses Evoked by Blockade of Excitatory Amino Receptors in the Rostral Ventrolateral Medulla in Spontaneously Hypertensive Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiovascular responses to injections of angiotensin II or carbachol into the rostral ventrolateral medulla in rats with AV3V lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Electrophysiological properties of rostral ventrolateral medulla presympathetic neurons modulated by the respiratory network in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central cholinergic blockade reduces the pressor response to L-glutamate into the rostral ventrolateral medullary pressor area

Injections of the excitatory amino acid L-glutamate (L-glu) into the rostral ventrolateral medulla (RVLM) directly activate the sympathetic nervous system and increase mean arterial pressure (MAP). A previous study showed that lesions of the anteroventral third ventricle region in the forebrain reduced the pressor response to L-glu into the RVLM. In the present study we investigated the effects produced by injections of atropine (cholinergic antagonist) into the lateral ventricle (LV) on the pressor responses produced by L-ghl into the RVLM. Male Holtzman rats (280-320 g, n=5 to 12/group) with stainless steel cannulas implanted into the RVLM, LV or 4th ventricle (4th V) were used. MAP and heart rate (HR) were recorded in unanesthetized rats. After saline into the LV, injections of L-glu (5 nmol/100 nl) into the RVLM increased MAP (51 +/- 4 mm Hg) without changes in HR. Atropine (4 nmol/1 PI) injected into the LV reduced the pressor responses to L-glu into the RVLM (36 +/- 5 mm Hg), However, atropine at the same dose into the 4th V or directly into the RVLM did not modify the pressor responses to L-glu into the RVLM (45 +/- 2 and 49 +/- 4 mm Hg, respectively, vs. control: 50 +/- 4mmHg). Central cholinergic blockade did not affect baro and chemoreflex nor the basal MAP and HR. The results suggest that cholinergic mechanisms probably from forebrain facilitate or modulate the pressor responses to L-glu into the RVLM. The mechanism is activated by acetylcholine in the forebrain, however, the neurotransmitter released in the RVLM to facilitate the effects of glutamate is not acetylcholine. (C) 2007 Elsevier B.V. All rights reserved.

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

A rise in arterial PCO(2) stimulates breathing and sympathetic activity to the heart and blood vessels. In the present study, we investigated the involvement of the retrotrapezoid nucleus (RTN) and glutamatergic mechanisms in the Botzinger/C1 region (Botz/C1) in these responses. Splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded in urethane-anesthetized, sino-aortic-denervated, vagotomized, and artificially ventilated rats subjected to hypercapnia (end-expiratory CO(2) from 5% to 10%). Phrenic activity was absent at end-expiratory CO(2) of 4%, and strongly increased when end-expiratory CO(2) reached 10%. Hypercapnia also increased sSND by 103 +/- 7%. Bilateral injections of the GABA-A agonist muscimol (2 mM) into the RTN eliminated the PND and blunted the sSND activation (Delta = +56 +8%) elicited by hypercapnia. Injections of NMDA receptor antagonist AP-5 (100 mM), non-NMDA receptor antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 100 mM) or metabotropic glutamate receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG; 100 mM) bilaterally into the Botz/C1 reduced PND (Delta = +43 +/- 7%, +52 +/- 6% or +56 +/- 11%, respectively). MCPG also reduced sSND (Delta = +41 +/- 7%), whereas AP-5 and DNQX had no effect. In conclusion, the increase in sSND caused by hypercapnia depends on increased activity of the RTN and on metabotropic receptors in the Botz/C1, whereas PND depends on increased RTN activity and both ionotropic and metabotropic receptors in the Botz/C1.

Role of catecholaminergic neurones of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats

Several findings suggest that catecholaminergic neurones in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. The present study sought to determine the effects of lesions of these neurones on the cardiovascular responses induced by changes in circulating volume. All experiments were performed in male Wistar rats (320-360 g). Medullary catecholaminergic neurones were lesioned by microinjection of anti-dopamine beta-hydroxylase-saporin (6.3 ng in 60 nl; SAP rats, n = 14) into the CVLM, whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n = 15). Two weeks later, rats were anaesthetized (urethane, 1.2 g kg(-1), I.V..), instrumented for measurement of mean arterial pressure (MAP), renal blood flow (RBF) and renal vascular conductance (RVC), and infused with hypertonic saline (HS; 3 M NaCl, 0.18 ml (100 g body weight)(-1), I.V.) or an isotonic solution (volume expansion, VE; 4% Ficoll, 1% of body weight, I.V.). In sham rats, HS induced sustained increases in RBF and RVC (155 +/- 7 and 145 +/- 6% of baseline, at 20 min after HS). In SAP rats, RBF responses to HS were blunted (125 +/- 6%) and RVC increases were abolished (108 +/- 5%) 20 min after HS. Isotonic solution increased RBF and RVC in sham rats (149 +/- 10 and 145 +/- 12% of baseline, respectively, at 20 min). These responses were reduced in SAP rats (131 +/- 6 and 126 +/- 5%, respectively, at 20 min). Pressor responses to HS were larger in SAP rats than in sham rats (17 +/- 5 versus 9 +/- 2 mmHg, at 20 min), whereas during VE these responses were similar in both groups (6 +/- 3 versus 4 +/- 6 mmHg, at 20 min). Immunohistochemical analysis indicates that microinjections of anti-D beta H-saporin produced extensive destruction within the A1/C1 cell groups in the CVLM. These results suggest that catecholaminergic neurones mediate the cardiovascular responses to VE or increases in plasma sodium levels.

Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata

The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the cardiovascular reflexes within the brainstem. It is well-known that one of the mechanisms by which angiotensin II exerts its effect is via the activation of pathways that generate reactive oxygen species (ROS). In the central nervous system, ROS are reported to be involved in several pathological diseases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.

Ventrolateral medulla mechanisms involved in cardiorespiratory responses to central chemoreceptor activation in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Contribution of the rostral ventromedial medulla to post-anxiety induced hyperalgesia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin-deficient (ob/ob) mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transcriptome analysis of nicotine-exposed cells from the brainstem of neonate spontaneously hypertensive and Wistar Kyoto rats

In this study, the effects of nicotine on global gene expression of cultured cells from the brainstem of spontaneously hypertensive rat (SHR) and normotensive Wistar Kyoto (WKY) rats were evaluated using whole-genome oligoarrays. We found that nicotine may act differentially on the gene expression profiles of SHR and WKY. The influence of strain was present in 321 genes that were differentially expressed in SHR as compared with WKY brainstem cells independently of the nicotine treatment. A total of 146 genes had their expression altered in both strains after nicotine exposure. Interaction between nicotine treatment and the strain was observed to affect the expression of 229 genes that participate in cellular pathways related to neurotransmitter secretion, intracellular trafficking and cell communication, and are possibly involved in the phenotypic differentiation between SHR and WKY rats, including hypertension. Further characterization of their function in hypertension development is warranted. The Pharmacogenomics Journal (2010) 10, 134-160; doi:10.1038/tpj.2009.42; published online 15 September 2009