INHIBITION OF NITRIC-OXIDE SYNTHESIS INCREASES BLOOD-PRESSURE IN HEALTHY HUMANS

Objective: To examine whether endogenous production of the endothelium -derived vasodilator nitric oxide influences blood pressure in healthy humans. Methods: After preliminary pilot dose-ranging studies, 3 mg/k g N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide syn thase, and saline placebo were infused intravenously over 5 min to eig ht healthy subjects in a two-phase, randomized, single-blind crossover study. Blood pressure and cardiac and renal function were measured. R esults: Compared with placebo, L-NMMA increased mean arterial pressure by 10%, decreased heart rate by 19%, decreased cardiac index by 25% a nd increased calculated total peripheral resistance by 46%. Effects we re maximal 10-15 min after starting L-NMMA infusion. Urinary sodium an d fractional sodium excretions were increased by L-NMMA, but creatinin e clearance was unchanged. Conclusions: Basal generation of nitric oxi de influences total peripheral resistance and blood pressure in health y humans. The natriuresis induced by L-NMMA may be related to the incr ease in blood pressure, or arise from inhibition of the intrarenal act ions of nitric oxide. Any decrease in nitric oxide generation, as has been postulated to occur in essential hypertension, could have substan tial effects on blood pressure and tissue blood flow.