Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits.
Dietary supplementation of L-arginine, the precursor of endogenous NO, has been shown to enhance endothelial function in the cholesterol-fed rabbits. However, the mechanism by which dietary L-arginine accomplishes these effects has been unclear. In the present study we have assessed the plasma concentrations of L-arginine and of asymmetrical dimethylarginine (ADMA), a known endogenous inhibitor of NO synthase, in cholesterol-fed rabbits with or without dietary supplementation of L-arginine. Urinary nitrate excretion rates were assessed as an index of endogenous NO formation. Plasma L-arginine levels were not different between control and cholesterol-fed rabbits, but they were elevated nearly threefold in rabbits fed cholesterol + L-arginine. Plasma ADMA concentration increased about two-fold in hypercholesterolemia, but was unaffected by dietary L-arginine. Thus, dietary L-arginine elevated the plasma L-arginine/ADMA ratio above the normal level, and partly restored urinary nitrate excretion, which was decreased by hypercholesterolemia. We conclude that elevation of the L-arginine/ADMA ratio may at least partly explain the restored NO formation by exogenous L-arginine in hypercholesterolemia.
Bode-Böger
S M
SM
Institute of Clinical Pharmacology, Medical School, Hannover, Germany.
Böger
R H
RH
Kienke
S
S
Junker
W
W
Frölich
J C
JC
D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D002791:Cholesterol, Dietary; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D005527:Food, Fortified; D006937:Hypercholesterolemia / Q000378:metabolism*; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012016:Reference Values
D002791:Cholesterol, Dietary; D009566:Nitrates; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase