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/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, and saline placebo were infused intravenously over 5 min to eight healthy subjects in a two-phase, randomized, single-blind crossover study. Blood pressure and cardiac and renal function were measured.


RESULTS
Compared with placebo, L-NMMA increased mean arterial pressure by 10%, decreased heart rate by 19%, decreased cardiac index by 25% and increased calculated total peripheral resistance by 46%. Effects were maximal 10-15 min after starting L-NMMA infusion. Urinary sodium and fractional sodium excretions were increased by L-NMMA, but creatinine clearance was unchanged.


CONCLUSIONS
Basal generation of nitric oxide influences total peripheral resistance and blood pressure in healthy humans. The natriuresis induced by L-NMMA may be related to the increase in blood pressure, or arise from inhibition of the intrarenal actions of nitric oxide. Any decrease in nitric oxide generation, as has been postulated to occur in essential hypertension, could have substantial effects on blood pressure and tissue blood flow.
Haynes
W G
WG
Department of Medicine, University of Edinburgh, Western General Hospital, UK.
Noon
J P
JP
Walker
B R
BR
Webb
D J
DJ
D000328:Adult; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase; D016037:Single-Blind Method; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases