Asymmetric dimethylarginine (ADMA) : A novel risk factor for endothelial dysfunction : Its role in hypercholesterolemia

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic a...

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Published in:Circulation (New York, N.Y.) N.Y.), 1998-11, Vol.98 (18), p.1842-1847
Main Authors: BÖGER, R. H, BODE-BÖGER, S. M, SZUBA, A, TSAO, P. S, CHAN, J. R, TANGPHAO, O, BLASCHKE, T. F, COOKE, J. P
Format: Article
Language:English
Subjects:
Arginine - analogs & derivatives
Arginine - blood
Arginine - therapeutic use
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Double-Blind Method
Endothelium, Vascular - physiopathology
Female
Humans
Hypercholesterolemia - blood
Hypercholesterolemia - drug therapy
Hypercholesterolemia - enzymology
Hypercholesterolemia - physiopathology
Injections, Intravenous
Male
Medical sciences
Middle Aged
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type III
Osmolar Concentration
Risk Factors
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Summary:Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic adults. We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind, placebo-controlled study, we investigated whether these changes could be reversed with exogenous L-arginine. We measured plasma levels of L-arginine, ADMA, and symmetrical dimethylarginine (SDMA) by high-performance liquid chromatography in 49 hypercholesterolemic (HC) and 31 normocholesterolemic (NC) humans. In 8 HC subjects, endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of L-arginine or placebo and compared with 8 NC control subjects. ADMA levels were significantly elevated by >100% (2.17+/-0.15 versus 1.03+/-0.09 micromol/L; P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.98.18.1842