title: The hypotensive effect of L-arginine is associated with increased expired nitric oxide in humans.
abstract: Endothelial metabolism of L-arginine to L-citrulline and the potent vasodilator, nitric oxide (NO), is important in the regulation of vascular tone and resting BP. L-arginine improves abnormal endothelium-dependent vasodilation in the setting of hypercholesterolemia and has a vasodilatory effect in normal vessels, effects presumed to be mediated through increased endogenous NO production, although this has not been established by direct measurement of NO. In a randomized, placebo-controlled, crossover trial, 10 healthy male subjects received a 30-min infusion of 0.5 g/kg L-arginine hydrochloride. Subjects underwent continuous monitoring of BP and heart rate (HR) as well as intermittent determination of mixed expired NO concentration and plasma L-arginine and L-citrulline levels. Infusion of L-arginine produced a significant fall in mean BP with a peak effect of -9.3 +/- 0.9% (p<0.005). The hemodynamic effects of L-arginine were associated with an increase in mixed expired NO concentration (FeNO) of 55 +/- 15% (p<0.005) from 15 +/- 2 to 21 +/- 3 parts per billion (ppb) and an increase in the rate of pulmonary NO excretion of 118 +/- 45% (p<0.005), as well as a rise in plasma L-citrulline from 25 +/- 4 to 46 +/- 5 micromol/l (p<0.005). There was a significant correlation between the hypotensive response to L-arginine and the increase in expired NO (r=-0.68, p<0.05). The hypotensive effect of L-arginine in humans appears to be mediated, at least in part, by NO synthase metabolism of L-arginine and increased endogenous NO production as indicated both by increased plasma L-citrulline and by increased expired NO.
authors.affiliation: Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: R D
authors.initials: RD
authors.lastname: Levy
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001944:Breath Tests; D002956:Citrulline / Q000097:blood; D018592:Cross-Over Studies; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine