LONG-TERM L-ARGININE SUPPLEMENTATION IMPROVES SMALL-VESSEL CORONARY ENDOTHELIAL FUNCTION IN HUMANS

Background-Coronary endothelial dysfunction is characterized by an imb alance between endothelium-derived vasodilating and vasoconstricting f actors and coronary vasoconstriction in response to the endothelium-de pendent vasodilator acetylcholine. Thus, the present double-blind, ran domized study was designed to test the hypothesis that long-term, 6-mo nth supplementation of L-arginine, the precursor of the endothelium-de rived vasodilator NO, reverses coronary endothelial dysfunction to ace tylcholine in humans with nonobstructive coronary artery disease. Meth ods and Results-Twenty-six patients without significant coronary arter y disease on coronary angiography and intravascular ultrasound were bl indly randomized to either oral L-arginine or placebo, 3 g TID. Endoth elium-dependent coronary blood flow reserve to acetylcholine (10(-6) t o 10(-4) mol/L) was assessed at baseline and after 6 months of therapy . There was no difference between the two study groups in clinical cha racteristics or in the coronary blood flow in the response to acetylch oline at baseline. After 6 months, the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group (149+/-20% versus 6+/-9%, P<0.05), Th is was associated with a decrease in plasma endothelin concentrations and an improvement in patients' symptoms scores in the L-arginine trea tment group compared with the placebo group. Conclusions-Long-term ora l L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant im provement in symptoms and a decrease in plasma endothelin concentratio ns. This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.