Long-term l-Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function in Humans
Background—Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of l-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease.
Methods and Results—Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly randomized to either oral l-arginine or placebo, 3 g TID. Endothelium-dependent coronary blood flow reserve to acetylcholine (10−6 to 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 characteristics or in the coronary blood flow in the response to acetylcholine 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). This was associated with a decrease in plasma endothelin concentrations and an improvement in patients’ symptoms scores in the l-arginine treatment group compared with the placebo group.
Conclusions—Long-term oral l-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations. This study proposes a role for l-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.
- Received October 14, 1997.
- Revision received January 21, 1998.
- Accepted January 23, 1998.
- Copyright © 1998 by American Heart Association