title: L-Arginine inhibits xanthine oxidase-dependent endothelial dysfunction in hypercholesterolemia.
abstract: 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.
authors.affiliation: 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
authors.forename: C Roger
authors.initials: CR
authors.lastname: White
authors.forename: Dale A
authors.initials: DA
authors.lastname: Parks
authors.forename: Rakesh P
authors.initials: RP
authors.lastname: Patel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shelton
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Tarpey
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Freeman
authors.forename: Victor M
authors.initials: VM
authors.lastname: Darley-Usmar
mesh_terms: 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*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D014969:Xanthine Oxidase; D000109:Acetylcholine