The Hypotensive Effect of L-Arginine Is Associated With Increased Expired Nitric Oxide in Humans

¹ From the Respiratory and Cardiology Divisions, Royal Victoria Hospital, and Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada

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 µmol/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.

Key Words: blood pressure • endothelium • endothelium-derived relaxing factor • nitric oxide synthase • vasodilation

Submitted on October 17, 1995
Accepted on January 29, 1996

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