Evidence for a role of nitric oxide in hindlimb vasodilation induced by hypothalamic stimulation in anesthetized rats

Electrical stimulation of the hypothalamus produces cardiovascular adjustments consisting of hypertension, tachycardia, visceral vasoconstriction and hindlimb vasodilation. Previous studies have demonstrated that hindlimb vasodilation is due a reduction of sympathetic vasoconstrictor tone and to activation of beta2-adrenergic receptors by catecholamine release. However, the existence of a yet unidentified vasodilator mechanism has also been proposed. Recent studies have suggested that nitric oxide (NO) may be involved. The aim of the present study was to investigate the role of NO in the hindquarter vasodilation in response to hypothalamic stimulation. In pentobarbital-anesthetized rats hypothalamic stimulation (100 Hz, 150µA, 6 s) produced hypertension, tachycardia, hindquarter vasodilation and mesenteric vasoconstriction. Alpha-adrenoceptor blockade with phentolamine (1.5 mg/kg, iv) plus bilateral adrenalectomy did not modify hypertension, tachycardia or mesenteric vasoconstriction induced by hypothalamic stimulation. Hindquarter vasodilation was strongly reduced but not abolished. The remaining vasodilation was completely abolished after iv injection of the NOS inhibitor L-NAME (20 mg/kg, iv). To properly evaluate the role of the mechanism of NO in hindquarter vasodilation, in a second group of animals L-NAME was administered before alpha-adrenoceptor blockade plus adrenalectomy. L-NAME treatment strongly reduced hindquarter vasodilation in magnitude and duration. These results suggest that NO is involved in the hindquarter vasodilation produced by hypothalamic stimulation.Em animais anestesiados a EE do hipotálamo produz um padrão de ajustes cardiovasculares caracterizado por hipertensão arterial, taquicardia, vasodilatação muscular e vasoconstrição mesentérica, entretanto, os mecanismos periféricos envolvidos nestes ajustes cardiovasculares ainda não foram completamente esclarecidos. O presente estudo teve como objetivo caracterizar os mecanismos periféricos responsáveis pela redistribuição de fluxo sanguíneo produzidas pela EE do hipotálamo. Os resultados obtidos demonstraram que 1) em ratos anestesiados a EE do hipotálamo produziu hipertensão arterial, taquicardia, vasoconstrição no leito mesentérico e acentuada vasodilatação dos membros posteriores; 2) a combinação do bloqueio farmacológico de receptores alfa1 e alfa2 adrenérgicos com fentolamina mais adrenalectomia bilateral reduziu a vasoconstrição mesentérica e a vasodilatação dos membros posteriores. Nestes animais o bloqueio da síntese de NO com L-NAME provocou nova redução significante da vasodilatação dos membros posteriores; 3) a administração de L-NAME, previamente o bloqueio farmacológico com fentolamina mais adrenalectomia bilateral, reduziu as respostas de vasoconstrição mesentérica e de vasodilatação dos membros posteriores. Estes resultados sugerem a existência de pelo menos três possíveis mecanismos responsáveis pela vasodilatação dos membros posteriores induzida pela EE do hipotálamo: 1) ativação de receptores beta-adrenérgicos por catecolaminas liberadas pela medula adrenal; 2) redução do tono vasoconstritor simpático e 3) um terceiro mecanismo que utiliza NO como mediador.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNIFESP-EPM Departamento de FisiologiaUNIFESP, EPM, Depto. de FisiologiaSciEL

Cardiovascular adjustments induced by hypertonic saline in hemorrhagic rats: Involvement of carotid body chemoreceptors

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline brings potential benefits to the treatment of hemorrhage. the neural mechanisms involved in these beneficial effects remain unknown. the present study examines the role of carotid chemoreceptors in cardiovascular responses induced by hypertonic saline after hypovolemic hemorrhage in rats. Male Wistar rats (300-400 g) were anesthetized with thiopental, and instrumented for recording of mean arterial pressure. Arterial pressure was reduced to 60 mm Hg by withdrawal of arterial blood over 10 min, and maintained at this level for 60 min by withdrawal or infusion of blood. in control rats (n = 8) with intact chemoreceptors, the subsequent intravenous infusion of hypertonic saline (3M NaCl, 1.8 ml kg(-1) body weight, in 2 min) restored blood pressure (pressure increased from 61 +/- 4 to 118 +/- 5 mm Hg). in experimental rats (n = 8), the carotid body arteries were tied, 30 min after the beginning of the hypotensive phase, leaving the carotid chemoreceptors ischemic. in these rats, hypertonic saline failed to restore blood pressure (pressure increased from 55 +/- 1 to 70 +/- 6 mm Hg). These findings suggest that the restoration of blood pressure after hypovolemic hemorrhage induced by hypertonic saline depends on intact carotid chemoreceptors. (C) 2010 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Goias, Dept Physiol Sci, Inst Ciencias Biol 2, BR-74001970 Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Physiol, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, Escola Paulista Med, São Paulo, BrazilCAPES: BEX1380/07-9Web of Scienc

Rostral ventrolateral medulla - A source of sympathetic activation in rats subjected to long-term treatment with L-NAME

The major aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats subjected to long-term treatment with N-G-nitro-L-arginine methyl ester (L-NAME) (70 mg/kg orally for 1 week). We inhibited or stimulated RVLM neurons with the use of drugs such as glycine, L-glutamate, or kynurenic acid in urethane-anesthetized rats (1.2 to 1.4 g/kg: IV). Bilateral microinjection of glycine (50 nmol. 100 nL) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 158+/-4 to 71+/-4 mm Hg (P<0.05), which was similar to the decrease produced by intravenous administration of hexamethonium. In normotensive rats, glycine microinjection reduced MAP from 106+/-4 to 60+/-3 mm Hg (P<0.05). Glutamate microinjection into the RVLM produced a significant increase in MAP in both hypertensive rats (from 157+/-3 to 201+/-6 mm Hg) and normotensive rats (from 105+/-5 to 148+/-9 mm Hg). No change in MAP was observed in response to kynurenic acid microinjection into the RVLM in either group. These results suggest that hypertension in response to long-term L-NAME treatment is dependent on an increase in central sympathetic drive, mediated by RVLM neurons. However, glutamatergic synapses within RVLM are probably not involved in this response.Univ Fed Sao Paulo, Escola Paulista Med, Dept Fisiol, BR-04023060 Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Fisiol, BR-04023060 Sao Paulo, BrazilWeb of Scienc

Importance of rostral ventrolateral medulla in the hypertension induced by acute or chronic inhibition of nitric oxide.

UNIFESP, Escola Paulista Med, Dept Physiol, BR-0402360 Sao Paulo, BrazilUNIFESP, Escola Paulista Med, Dept Physiol, BR-0402360 Sao Paulo, BrazilWeb of Scienc

Importance of rostral ventrolateral medulla in the hypertension induced by acute or chronic inhibition of nitric oxide.

UNIFESP, Escola Paulista Med, Dept Physiol, BR-04023060 Sao Paulo, BrazilUNIFESP, Escola Paulista Med, Dept Physiol, BR-04023060 Sao Paulo, BrazilWeb of Scienc