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L ‐Arginine inhibits xanthine oxidase‐dependent endothelial dysfunction in hypercholesterolemia
Author(s) -
White C.Roger,
Parks Dale A.,
Patel Rakesh P.,
Shelton Jonathan,
Tarpey Margaret M.,
Freeman Bruce A.,
Darley-Usmar Victor M.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00137-1
Subject(s) - xanthine oxidase , arginine , endothelial dysfunction , endocrinology , medicine , superoxide , chemistry , acetylcholine , xanthine , nitric oxide , biochemistry , biology , enzyme , amino acid
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.