Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina - Lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance

OBJECTIVES This study was designed to determine the effect of two weeks' tr eatment with L-arginine on the ratio of plasma L-arginine to asymmetric dim ethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatatio n to acetylcholine, exercise performance and heart rate variability in men with stable angina. BACKGROUND The ratio of plasma L-arginine:ADMA has been proposed as a deter minant of endothelium-dependent dilation; dietary supplementation with L-ar ginine has been shown to improve endothelium-dependent vasodilation and sym ptoms in some conditions. METHODS Men (n = 40) with stable angina, at least one epicardial coronary a rtery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a dou ble-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostagland in F-2 alpha (a marker of oxidative stress) and forearm vasodilator respons es to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arg inine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period. RESULTS Plasma L-arginine increased after oral L-arginine, whereas ADMA rem ained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acety lcholine response by infra-arterial L-arginine at baseline, this response r emained unchanged after oral L-arginine. Measures of oxidative stress and e xercise performance after L-arginine/placebo were similar in placebo and ac tive groups. CONCLUSIONS In men with stable angina, an increase in plasma L-arginine/ADM A ratio after two weeks' oral supplementation with L-arginine is not associ ated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance. {J Am Coll Cardiol 2001; 38:499-505) (C) 2 001 by the American College of Cardiology.