ORAL L-ARGININE IMPROVES ENDOTHELIUM-DEPENDENT DILATION IN HYPERCHOLESTEROLEMIC YOUNG-ADULTS

In hypercholesterolemic rabbits, oral L-arginine (the substrate for en dothelium derived nitric oxide) attenuates endotheliai dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown, Using high resolution external ultrasound, we studied arteria l physiology in 27 hypercholesterolemic subjects aged 29 +/- 5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238 +/- 43 mg/dl, Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study, Brachial artery diameter w as measured at rest, during increased flow (causing endothelium-depend ent dilation, EDD) and after sublingual glyceryl trinitrate (causing e ndothelium-independent dilation), After oral L-arginine, plasma L-argi nine levels rose from 115 +/- 103 to 231 +/- 125 mu mol/liter (P < 0.0 01), and EDD improved from 1.7 +/- 1.3 to 5.6 +/- 3.0% (P < 0.001), In contrast there was no significant change in response to glyceryl trin itrate, After placebo there were no changes in endothelium-dependent o r independent vascular responses. Lipid levels were unchanged after L- arginine and placebo, Dietary supplementation with L-arginine signific antly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.