ADMA: its role in vascular disease.
Endothelium-derived nitric oxide (NO) is the most potent endogenous vasodilator and, by virtue of its anti-inflammatory and anti-thrombotic effects, it is an endogenous anti-atherogenic agent. Accordingly, impairment of NO synthesis or bioactivity may increase the risk of vascular disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the NO synthase pathway. Plasma levels of ADMA are increased in patients with vascular disease, or with risk factors for vascular disease. Preclinical and clinical studies indicate that ADMA may mediate the adverse effects of traditional risk factors on endothelial vasodilator function. By impairing endothelial function, ADMA may contribute to pulmonary or systemic hypertension, as well as to vascular disease. Several drugs known to treat cardiovascular disease also reduce plasma ADMA levels, such as angiotensin receptor antagonists, converting enzyme inhibitors, and insulin sensitizing agents. Plasma ADMA may be a common mediator of endothelial dysfunction induced by vascular risk factors. Insights into the mechanisms by which plasma ADMA is regulated may lead to new therapeutic knowledge.
Cooke
John P
JP
Division of Cardiovascular Medicine, Stanford University School of Medicine, Falk Cardiovascular Research Center, CA 94305-5406, USA. john.cooke@stanford.edu
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012307:Risk Factors
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C059999:dimethylargininase