HEMODYNAMIC AND SYMPATHETIC EFFECTS OF INHIBITION OF NITRIC-OXIDE SYNTHASE BY SYSTEMIC INFUSION OF N-G-MONOMETHYL-L-ARGININE INTO HUMANS ARE DOSE-DEPENDENT

Background In several animal species, nitric oxide (NO) buffers centra l neural sympathetic outflow, but data concerning humans are sparse an d conflicting. We hypothesized that these conflicting results could be related to large differences in the dose of NG. monomethyl-L-arginine , a stereospecific inhibitor of NO synthase, infused in these human st udies. Objective To investigate the haemodynamic and sympathetic effec ts of systemic inhibition of NO synthase by intravenous infusion of tw o different doses of N-G-menomethyl-L-arginine into healthy humans and compare these effects with those of an equipressor dose of the non-en dothelium-dependent vasoconstrictor phenylephrine. Methods Muscle symp athetic nerve activity was measured by microneurography and blood flow by venous occlusion plethysmography, N-G-monomethyl-L-arginine was in fused over 15 min at a rate of 50 mu g/kg per min into members of one group (n = 8) and at a rate of 450 mu g/kg per min into members of ano ther group (n = 7), An equipressor dose of phenylephrine was infused i nto four subjects from each group. Results Infusions of N-G-monomethyl -L-arginine and of phenylephrine at the higher dose similarly suppress ed sympathetic activity. In contrast, infusions of NG. monomethyl-L-ar ginine and of an equipressor dose of phenylephrine at the lower dose h ad different sympathetic effects. Burst frequency of muscle sympatheti c nerve activity remained unchanged during infusion of N-G-monomethyl- L-arginine but decreased by roughly 50% during infusion of phenylephri ne, Infusion of N-G-monomethyl-L-arginine at both doses did not alter forearm blood flow, Only infusion of N-G-monomethyl-L-arginine at the higher dose increased forearm vascular resistance. Conclusions Haemody namic and sympathetic effects of inhibition of NO synthase by infusion of N-G-monomethyl-L-arginine into humans are dose dependent At higher doses, N-G-monomethyl-L-arginine exerts sympathoinhibitory effects th at are comparable to those evoked by a non-specific vasoconstrictor dr ug, whereas at lower doses, it exerts sympatho-excitatory effects. (C) 1998 Lippincott-Raven Publishers.