Endothelial dysfunction in hypercholesterolemia is improved by L-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. L-arginine improves endothelial function in hypercholesterolemic subjects. The goal of the present study was to investigate the effects of L-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 L-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 L-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. L-arginine improves endothelial function with decreasing oxidative stress. The augmentation of nitric oxide production/release induced by L-arginine may act as an antioxidant, and contributes to the improvement of endothelial function in hypercholesterolemic subjects.
Kawano
Hiroaki
H
Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City 860-8556, Japan. koumei@gpo.kumamoto-u.ac.jp
Motoyama
Takeshi
T
Hirai
Nobutaka
N
Kugiyama
Kiyotaka
K
Yasue
Hirofumi
H
Ogawa
Hisao
H
D000328:Adult; D000704:Analysis of Variance; D001120:Arginine / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D015588:Observer Variation; D018384:Oxidative Stress / Q000502:physiology*; D011336:Probability; D012016:Reference Values; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001120:Arginine