INHIBITION OF SYMPATHETIC VASOCONSTRICTION IS A MAJOR PRINCIPLE OF VASODILATION BY NITRIC-OXIDE IN-VIVO

The objective of this study was to determine whether vasodilator effec ts of nitric oxide (NO) can be explained by the inhibition of vasocons triction caused by peripheral sympathetic nerve activity (SNA) in vivo . For this purpose, we studied the effects of systemic inhibition of N O 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 H g that were associated with slight decreases in preganglionic SNA reco rded from the white ramus of the third thoracic segment. Higher SNA ap peared in completely baroreceptor-denervated cats (n=10) than in the i ntact cats, but no changes in nerve activity occurred after the subseq uent administration of L-NAME. In contrast, MAP increased from 123.3 /- 4.0 to 245.8 +/- 5.1 mm Hg. In baroreceptor-denervated cats, revers ible suppression of peripheral SNA produced by cooling of the ventral surface of the rostral ventrolateral medulla oblongata (RVLM) caused s ignificant hypotension (61.1 +/- 2.6 mm Hg) and almost completely reve rsed the hypertension caused by L-NAME (76.0 +/- 3.7 mmHg). Intravenou s administration of the alpha(1)-adrenergic receptor antagonist prazos in after L-NAME reduced MAP to a similar extent. In contrast, hyperten sion induced by angiotensin II could not be reversed by RVLM cooling. The presser effects of intravenously administered noradrenaline during RVLM cooling were markedly potenti ated by L-NAME and attenuated by t he NO-donor compound S-nitroso-N-acetylpenicillamine (SNAP). These res ults demonstrate that inhibition of peripheral sympathetic vasoconstri ction is an important mechanism of vasodilation by NO in vivo and sugg est that the vascular effects of NO may be very closely linked to the regulation of cardiovascular functions by the central nervous system.