title: The pharmacodynamics of L-arginine.
abstract: L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes called NO synthases (NOSs). In the brain, NO acts as a neurotransmitter; in the immune system, it acts as a mediator of host defense; and in the cardiovascular system, it mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous, antiatherogenic molecule. About 5 g of L-arginine are ingested each day in a normal Western diet. Plasma levels of L-arginine are not significantly reduced in most diseases, except in end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or dietary (oral) administration of relatively large doses of L-arginine has been shown to result in enhanced NO formation in individuals with impaired endothelial function at baseline. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. However, in other trials, L-arginine was not beneficial, and in a recent study, the authors reported higher mortality for participants receiving L-arginine than for those receiving placebo. Recently, it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-Arginine metabolism by NOS, may determine an individual's response to L-arginine supplementation. L-Arginine appears to exert no effect in individuals with low ADMA levels, whereas in those with high levels, L-arginine restores the L-arginine/ADMA ratio to normal and, thereby, normalizes endothelial function. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Doses of 3-8 g/d appear to be safe and not to cause acute pharmacologic effects in humans.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000517:prevention & control*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism
chemical_list: C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase