Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo

Abstract

The objective of this study was to determine whether vasodilator effects of nitric oxide (NO) can be explained by the inhibition of vasoconstriction caused by peripheral sympathetic nerve activity (SNA) in vivo. For this purpose, we studied the effects of systemic inhibition of NO synthesis during experimental variation of SNA in anesthetized cats. Intravenous infusion of N(G)-nitro-L-arginine, methyl ester (L-NAME, 10 mg/kg) in baroreceptor- intact animals (n=6) caused increases in mean arterial blood pressure (MAP) from 105.8±3.4 to 192.0±4.3 mm Hg that were associated with slight decreases in preganglionic SNA recorded from the white ramus of the third thoracic segment. Higher SNA appeared in completely baroreceptor-denervated cats (n=10) than in the intact cats, but no changes in nerve activity occurred after the subsequent administration of L-NAME. In contrast, MAP increased from 123.3±4.0 to 245.8±5.1 mm Hg. In baroreceptor-denervated cats, reversible suppression of peripheral SNA produced by cooling of the ventral surface of the rostral ventrolateral medulla oblongata (RVLM) caused significant hypotension (61.1±2.6 mm Hg) and almost completely reversed the hypertension caused by L-NAME (76.0±3.7 mm Hg). Intravenous administration of the α1-adrenergic receptor antagonist prazosin after L-NAME reduced MAP to a similar extent. In contrast, hypertension induced by angiotensin II could not be reversed by RVLM cooling. The pressor effects of intravenously administered noradrenaline during RVLM cooling were markedly potentiated by L-NAME and attenuated by the NO-donor compound S-nitroso-N- acetylpenicillamine (SNAP). These results demonstrate that inhibition of peripheral sympathetic vasoconstriction is an important mechanism of vasodilation by NO in vivo and suggest that the vascular effects of NO may be very closely linked to the regulation of cardiovascular functions by the central nervous system.