L-Arginine inhibits xanthine oxidase-dependent endothelial dysfunction in hypercholesterolemia.
Xanthine oxidase (XO)-derived superoxide contributes to endothelial dysfunction in humans and animal models of hypercholesterolemia (HC). Since L-arginine supplementation prevents defects in NO signaling, we tested the hypothesis that L-arginine blunts the inhibitory effect of XO on vascular function. Acetylcholine-mediated relaxation was significantly impaired in ring segments of HC rabbits, a response that was associated with an increase in plasma XO activity. L-Arginine treatment of HC rabbits reduced plasma XO and improved endothelial function. L-Arginine also modestly prolonged the lag time for oxidation in isolated lipoprotein samples. These results reveal that the principal action of L-arginine is to protect against the XO-dependent inactivation of NO in arteries of HC rabbits.
White
C Roger
CR
Department of Medicine, Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 1046 Zeigler Research Building, 703 South 19th St., Birmingham, AL 35294-0007, USA. crwhite@uab.edu
Parks
Dale A
DA
Patel
Rakesh P
RP
Shelton
Jonathan
J
Tarpey
Margaret M
MM
Freeman
Bruce A
BA
Darley-Usmar
Victor M
VM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D014969:Xanthine Oxidase / Q000097:blood / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D014969:Xanthine Oxidase; D000109:Acetylcholine