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.
RCT Entities:
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.
Authors: Carl J Pepine; Keith C Ferdinand; Leslee J Shaw; Kelly Ann Light-McGroary; Rashmee U Shah; Martha Gulati; Claire Duvernoy; Mary Norine Walsh; C Noel Bairey Merz Journal: J Am Coll Cardiol Date: 2015-10-27 Impact factor: 24.094
Authors: Kevin S Heffernan; Christopher A Fahs; Sushant M Ranadive; Eshan A Patvardhan Journal: J Cardiovasc Pharmacol Ther Date: 2010-01-06 Impact factor: 2.457