IMPORTÂNCIA DA REGIÃO ANTEROVENTRAL DO TERCEIRO VENTRÍCULO (AV3V) NO CONTROLE CARDIOVASCULAR E DO EQUILÍBRIO HIDROELETROLÍTICO

A manutenção da pressão arterial em níveis normais é importante para a homeostasia do meio interno. O sistema nervoso central regulando a atividade dos eferentes autonômicos simpático e parassimpático ajusta a pressão arterial possibilitando ao animal ou ao ser humano um melhor desempenho frente a diferentes situações do cotidiano. Diferentes áreas centrais são responsáveis pelo controle das descargas autonômicas sobre o sistema cardiovascular e muitas delas também participam do controle do equilíbrio hidroeletrolítico. Uma dessas áreas é o tecido periventricular ao redor da porção anteroventral do terceiro ventrículo (região AV3V) localizado no prosencéfalo e que é uma das principais áreas centrais onde se localizam receptores da angiotensina II e osmorreceptores. A lesão da região AV3V impede o desenvolvimento de diversas formas de hipertensão experimental em ratos e dificulta o aparecimento de respostas pressoras produzidas por diversos estímulos. A lesão da região AV3V também reduz respostas dipsogênicas induzidas pela angiotensina II, estimulação colinérgica central, privação hídrica e aumento de osmolaridade plasmática, a secreção do peptídeo natriurético atrial produzida pela expansão de volume e a excreção renal de sódio produzida pela estimulação colinérgica central. Evidências mais recentes também sugerem uma participação da região AV3V nas respostas pressoras produzidas pela ativação de mecanismos bulbares.The maintenance of the arterial pressure in normal levels is important for the homeostasis of body fluids. The central nervous system regulating sympathetic and parasympathetic autonomic efferent can adjust arterial pressure which allows animals or human to face different daily activities with the best performance. Different central areas are responsible for the control of autonomic discharges to cardiovascular system and many of them are also involved in the control of fluid electrolyte balance. One of these areas is the tissue surrounding the anteroventral third ventricle (AV3V region) localized in the forebrain and a main central site for angiotensin II receptors and osmoreceptors. The AV3V lesions impair the development of many models of experimental hypertension in rats and the pressor responses to different stimuli. Lesions of the AV3V region also reduce dipsogenic responses to angiotensin II, central cholinergic activation, water deprivation and increase in plasma osmolarity, atrial natriuretic peptide secretion produced by body fluid expansion and the increase in renal excretion to central cholinergic activation. Recent evidence also suggests the participation of AV3V region in pressor responses produced by the  activation of medullary mechanisms

ESPÉCIES REATIVAS DE OXIGÊNIO NO CONTROLE NEUROVEGETATIVO DA PRESSÃO ARTERIAL

The control of the blood pressure depends on the activity of select groups of neurons present in the central nervous system. Evidence has demonstrated that the redox state (a balance between oxidizing and reducing species) is involved in the control of neuronal activity, which suggests that the redox state can influence the neuronal transmission within the central nervous system acting on the neuronal modulation of biological functions. For instance, the glutamatergic transmission may be widely affected by reactive oxygen species, oxidizing agents that have been extensively investigated due to their involvement in physiological and pathological processes. In the present article, we discuss the main experimental finds that support the hypothesis that reactive oxygen species have important role in physiological (and pathological) modulation of the cardiovascular function through alterations in the sympathetic and parasympathetic system. Therefore, reactive oxygen species can actively participate in the development of cardiovascular diseases like hypertension when the balance in the redox state is disrupted.Existem evidências de que a atividade neuronal pode ser modulada pelo estado redox (balanço entre espécies químicas oxidantes e redutoras) das células, influenciando, assim, as diferentes funções biológicas que são controladas pelo sistema nervoso. Essa modulação pode ocorrer por meio de diferentes mecanismos e um deles é a modulação da transmissão sináptica no sistema nervoso central (SNC). As descargas autonômicas que são controladas por mecanismos localizados em diferentes áreas do SNC são fundamentais para o controle da pressão arterial. Um importante neurotransmissor que participa dos mecanismos centrais de controle cardiovascular é o glutamato e a transmissão glutamatérgica pode ser extensamente afetada por espécies reativas de oxigênio, oxidantes que parecem ter um importante papel em processos fisiológicos e patológicos. No presente artigo são apresentados os principais achados experimentais que suportam a hipótese de que as espécies reativas de oxigênio podem modular as funções cardiovasculares por produzir alterações nos mecanismos centrais de controle dos sistemas simpático e parassimpático. Logo, desequilíbrios na sinalização mediada por espécies reativas de oxigênios podem contribuir para o desenvolvimento de doenças cardiovasculares como a hipertensão

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1 mu l and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mu g/mu l) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/mu l) after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat

Activation of central α(2)-adrenoceptors mediates salivary gland vasoconstriction

OBJECTIVE:\ud Peripheral treatment with the cholinergic agonist pilocarpine increases salivary gland blood flow and induces intense salivation that is reduced by the central injection of moxonidine (α(2)-adrenoceptors/imidazoline agonist). In the present study, we investigated the effects of the intracerebroventricular (i.c.v.) injection of pilocarpine alone or combined with moxonidine also injected i.c.v. On submandibular/sublingual gland (SSG) vascular resistance. In addition, the effects of these treatments on arterial pressure, heart rate and on mesenteric and hindlimb vascular resistance were also tested.\ud \ud DESIGN:\ud Male Holtzman rats with stainless steel cannula implanted into lateral ventricle and anaesthetized with urethane+α-chloralose were used.\ud \ud RESULTS:\ud Pilocarpine (500nmol/1μl) injected i.c.v. Reduced SSG vascular resistance and increased arterial pressure, heart rate and mesenteric vascular resistance. Contrary to pilocarpine alone, the combination of moxonidine (20nmol/1μl) and pilocarpine injected i.c.v. Increased SSG vascular resistance, an effect abolished by the pre-treatment with the α(2)-adrenoceptor antagonist yohimbine (320nmol/2μl). The increase in arterial pressure, heart rate and mesenteric resistance was not modified by the combination of moxonidine and pilocarpine i.c.v.\ud \ud CONCLUSION:\ud These results suggest that the activation of central α(2)-adrenoceptors may oppose to the effects of central cholinergic receptor activation in the SSG vascular resistance.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq/PRONEX

Ingestion of hypertonic NaCl vs. palatable drinks by sodium-depleted rats

This work investigated whether the preference for NaCl solution is shifted to more palatable solutions in the adult male sodium-depleted rat (n=6-10 per group). Animals had daily access to three bottles, one containing water, another 1.8% NaCl (300 mM), and a third containing 0.9% NaCl (150 mM), Gatorade (orange-OG or grape flavored-GG), orange juice (sweetened or unsweetened, from concentrate), or 10% sucrose (no sodium). Sodium content in Gatorade and orange juice ranged from 7 to 14 mEq/l. Daily intakes were recorded for at least 5 days prior to sodium depletion. Then, the animals were depleted of sodium (diuretic plus sodium-deficient diet and water for 24 h). Then, the other two bottles were returned to the animals and the intakes were recorded for 120 min (sodium preference test, SPT). Daily intake from the third bottle (except for unsweetened orange juice) at least doubled the daily 1.8% NaCl intake. The average 1.8% NaCl intake (13 +/- 2 ml) in the SPT was higher than the intake of 10% sucrose (6 +/- 1 ml) or of any other solution (less than 6 ml). The intakes of 1.8% NaCl and 0.9% NaCl (10 +/- 3 ml) were similar during the SPT. The animals also preferred 0.9% NaCl (27 +/- 1 ml) to OG (3 +/- 1 ml) in the absence of 1.8% NaCl in the SPT. Therefore, the preference for sodium in sodium-depleted rats also applies when palatable and nutritive solutions are simultaneously available. (C) 2002 Elsevier B.V. All rights reserved

Cardiovascular responses to hydrogen peroxide into the nucleus tractus solitarius

The nucleus tractus solitarius (NTS), a major hindbrain area involved in cardiovascular regulation, receives primary afferent fibers from peripheral baroreceptors and chemoreceptors. Hydrogen peroxide (H2O2) is a relatively stable and diffusible reactive oxygen species (ROS), which acting centrally, may affect neural mechanisms. In the present study, we investigated effects of H2O2 alone or combined with the glutamatergic antagonist kynurenate into the NTS on mean arterial pressure (MAP) and heart rate (HR). Conscious or anesthetized (urethane and α-chloralose) male Holtzman rats (280–320 g) were used. Injections of H2O2 (125 to 1500 pmol/40 nl) into the intermediate NTS of anesthetized rats evoked dose-dependent and transient hypotension (−18 ± 3 to −55 ± 11 mmHg) and bradycardia (−16 ± 5 to −116 ± 40 bpm). Injection of the catalase inhibitor 3-amino-1,2,4-triazole (100 nmol/40 nl) into the NTS also produced hypotension and bradycardia. Previous injection of the ionotropic l-glutamate receptor antagonist kynurenate (7 nmol/40 nl) attenuated by 48% the bradycardic response, without changing the hypotension evoked by H2O2 (500 pmol/40 nl) in anesthetized rats. The antioxidant l-ascorbate (600 pmol/80 nl) injected into the NTS attenuated the bradycardic (42%) and hypotensive (67%) responses to H2O2 (500 pmol/40 nl) into the NTS. In conscious rats, injection of H2O2 (50 nmol/100 nl) into the NTS also evoked intense bradycardia (−207 ± 8 bpm) and hypotension (−54 ± 6 mmHg) that were abolished by prior injection of kynurenate (7 nmol/100 nl). The results show that H2O2 into the NTS induces hypotension and bradycardia probably due to activation of glutamatergic mechanisms

Sodium intake, brain c-Fos protein and gastric emptying in cell-dehydrated rats treated with methysergide into the lateral parabrachial nucleus

Previous studies from our laboratory have shown that methysergide, a serotonergic antagonist, injected into the lateral parabrachial nucleus (LPBN) combined with a pre-load of 2 M NaCl, given by gavage, induces 0.3 M NaCl intake. The mechanisms involved in this paradoxical behavior are still unknown. In the present work, we investigated the effect of serotonergic blockade into the LPBN on hindbrain and hypothalamic activity, gastric emptying and arterial blood pressure in cell-dehydrated rats. Methysergide plus 2 M NaCl infused intragastrically or intravenously promoted 0.3 M NaCl intake in two-bottle tests. In cell-dehydrated rats with no access to fluids, methysergide compared to vehicle increased Fos immunoreactivity in the medial nucleus of the solitary tract, area postrema and non-oxytocinergic cells of the ventral portion of the hypothalamic paraventricular nucleus (PVN). There was no alteration in the number of neurons double-labeled for Fos-ir and oxytocin in the PVN and supraoptic nuclei. There was also no alteration in plasma oxytocin and vasopressin, or arterial pressure. In rats cell-dehydrated by i.v. 2 M NaCl, methysergide also did not change the amount of an intragastric load of 0.3 M NaCl retained in the stomach or intestine. The results suggest that methysergide injected into the LPBN of cell-dehydrated rat does not alter primary inhibitory signals that control sodium intake. The inhibitory signals blocked by methysergide in the LPBN possibly originated from activation of brain osmoreceptors, second order visceral/hormonal signals or a combination of both.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP