Endothelial dysfunction in hypercholesterolemia is improved by -arginine administration: possible role of oxidative stress

Hypercholesterolemia impairs endothelial function. However, the production/release of nitric oxide from the hypercholesterolemic aorta is reported to be enhanced rather than impaired in animal studies. -arginine improves endothelial function in hypercholesterolemic subjects. The goal of the present study was to investigate the effects of -arginine on endothelial function and oxidative stress in hypercholesterolemic subjects. In 17 hypercholesterolemic male subjects (mean age 41.7 years, mean total cholesterol 264.3±5.9 mg/dl) and 17 age-matched healthy men as controls (mean total cholesterol 187.1±6.8 mg/dl), we measured flow-mediated endothelium-dependent vasodilation of the brachial artery during saline infusion and after saline plus -arginine infusion (30 g for 1 h) with ultrasound technique. In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS), as a marker of lipid peroxide. The flow-mediated vasodilation was lower and the TBARS concentration was higher in the hypercholesterolemic group than in the control group during the saline infusion. The addition of -arginine increased flow-mediated vasodilation and decreased TBARS concentration in the hypercholesterolemic group (from 3.92±0.58 to 7.27±0.53% [P<0.01 by analysis of variance (ANOVA)], from 7.74±0.46 to 5.71±0.35 nmol/ml [P<0.01 by ANOVA], respectively), but not in the control group (from 7.74±0.40 to 8.21±0.47%, from 5.45±0.43 to 4.83±0.35 nmol/ml, respectively). The endothelial function is blunted, and the oxidative stress is increased in hypercholesterolemic subjects. -arginine improves endothelial function with decreasing oxidative stress. The augmentation of nitric oxide production/release induced by -arginine may act as an antioxidant, and contributes to the improvement of endothelial function in hypercholesterolemic subjects.