Role of nitrosyl factors in the hindlimb vasodilation elicited by baroreceptor afferent nerve stimulation.

This study determined whether electrical stimulation (ES) of the baroreceptor afferent fibers in the aortic depressor nerve (ADN) produces hindlimb vasodilation in pentobarbital-anesthetized rats via the release of nitric oxide (NO)-containing (nitrosyl) factors from NO synthase-positive lumbar sympathetic nerve terminals. ES of the ADN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindlimb vascular resistance (MR and HLR, respectively). The falls in resistance were substantially smaller in hindlimb beds in which the ipsilateral lumbar sympathetic chain had been transected 7-10 days previously. The maximal falls in MR and hindquarter vascular resistance (HQR) produced by 1- to 10-Hz ES of the ADN were unaffected by the specific inhibitor of neuronal NO synthase 7-nitroindazole (7-NI, 45 mg/kg iv). However, the total falls in HQR (mmHg.kHz(-1).s) produced by these stimuli were significantly diminished by 7-NI, whereas the total falls in MR were not affected. Four successive episodes of 10-Hz ES produced equivalent reductions in MAP, MR, and HQR. The peak changes in these parameters were not affected by 7-NI. However, the total falls in HQR progressively diminished with each successive stimulus, whereas the total falls in MR remained unchanged. These results provide evidence that the hindlimb vasodilation produced by ES of baroreceptor afferents within the ADN may involve the activation of postganglionic lumbar sympathetic vasodilator fibers, which release newly synthesized and preformed nitrosyl factors.

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

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 a1 e a2 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 b-adrenérgicos por catecolaminas liberadas pela medula adrenal; 2) redução do tono vasoconstritor simpático e 3) um terceiro mecanismo que utiliza NO como mediador.

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, 150 microA, 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.

The effects of adrenalectomy in blood flow adjustments produced by sciatic nerve stimulation in rats.

Sciatic nerve stimulation (SNS) produces hypertension, tachycardia, vasodilatation in the stimulated limb and vasoconstriction in the limb contralateral to the stimulation site. These autonomic adjustments represent an equivalent of the cardiovascular responses described as features of defense-alerting reactions. However, while the muscle vasodilatation observed in rats during stimulation of hypothalamic sites involved in defense reactions has been referred to as a general, non-selective increase in blood flow, previous studies conducted on cats have demonstrated that high-intensity cutaneus stimulation produces vasodilatation in the stimulated limb and vasoconstriction in the other limbs. In anesthetized rats, the effects of SNS in the muscle vascular territory of the contralateral limb, as well as the participation of circulating catecholamines in these adjustments continued to be unknown. Therefore, in the present study we investigated the blood flow adjustments elicited by SNS in the stimulated and in the contralateral hind limbs before and after bilateral adrenalectomy. In urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (800-1000 microA, 1 ms, 100 Hz, 10 s) produced hypertension, tachycardia, vasodilatation in the stimulated hindlimb and vasoconstriction in the contralateral hindlimb. After bilateral adrenalectomy the pressor responses to SNS were abolished, the vasodilatation in the stimulated limb was greater and the vasoconstriction in the contralateral limb was replaced by vasodilatation. These results suggest that the vasodilatation in the stimulated limb does not depend on circulating catecholamines.

Rostral ventrolateral medulla: an integrative site for muscle vasodilation during defense-alerting reactions.

1. Evidence gathered over the last 30 years has firmly established that the rostral ventrolateral medulla (RVLM) is a major vasomotor center in the brainstem, harboring sympathetic premotor neurons responsible for generating and maintaining basal vasomotor tone and resting levels of arterial blood pressure. Although the RVLM has been almost exclusively classified as a vasopressor area, in this report we review some evidence suggesting a prominent role of the RVLM in muscle vasodilation during defense-alerting responses. 2. Defense-alerting reactions are a broad class of behavior including flexion of a limb, fight/flight responses, apologies, etc. They comprise species-distinctive motor and neurovegetative adjustments. Cardiovascular responses include hypertension, tachycardia, visceral vasoconstriction, and muscle vasodilation. Since defense-alerting reactions generally involve intense motor activation, muscle vasodilation is regarded as a key feature of these responses 3. In anesthetized or unanesthetized-decerebrate animals, natural or electrical stimulation of cutaneous and muscle afferents produced hypertension, tachycardia, and vasodilation restricted to the stimulated limb. 4. Unilateral inactivation of the RVLM contralateral to the stimulated limb abolished cardiovascular adjustments to stimulation of cutaneous and muscle afferents. Within the RVLM glutamatergic synapses mediate pressor responses, whereas GABAergic synapses mediates muscle vasodilation. 5. In urethane-anesthetized rats, electrical stimulation of the hypothalamus elicited hypertension, tachycardia, visceral vasoconstriction, and hindlimb vasodilation. The hindlimb vasodilation induced by hypothalamic stimulation is a complex response, involving reduction of sympathetic vasoconstrictor tone, release of catecholamines by the adrenal medulla, and a still unknown system that may use nitric oxide as a mediator. 6. Blockade of glutamatergic transmission within the RVLM selectively blocks muscle vasodilation induced by hypothalamic stimulation. 7. The results obtained suggest that, besides its role in the generation and maintenance of the sympathetic vasoconstrictor drive, the RVLM is also critical for vasodilatory responses during defense reactions. The RVLM may contain several, distinctive mechanisms for muscle vasodilation. Anatomical and functional characterization of these pathways may represent a breakthrough in our understanding of cardiovascular control in normal and/or pathological conditions.