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• W1989656393 abstract "Over the past 10 years nitric oxide has emerged as a vital signalling molecule in virtually every organ system. 1 Furchgott RF The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA. 1996; 276: 1186-1188 Crossref PubMed Google Scholar This gaseous mediator is synthesised from the aminoacid L-arginine by the action of nitric-oxide synthases, a family of enzymes with endothelial, neuronal, and inducible isoforms. 1 Furchgott RF The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA. 1996; 276: 1186-1188 Crossref PubMed Google Scholar In the cardiovascular system endothelium-derived nitric oxide exerts a tonic vasodilator tone, prevents cellular adhesion to the vessel wall, inhibits platelet activation, and retards the development of atherosclerosis in experimental models. In the brain it modulates neurotransmission but in excess can cause neurodegeneration. In the peripheral nervous system nitric oxide regulates pain perception and is a mediator of non-adrenergic non-cholinergic neurotransmission in the gut, genitourinary system, and vasculature. In the immune system nitric oxide is a mediator of cytotoxicity and a regulator of immune-cell function. Synthesis of nitric oxide from L-arginine can be blocked pharmacologically by NG-monomethyl-L-arginine (L-NMMA), a structural analogue of arginine that has been widely used experimentally to elucidate the functions of nitric oxide. 1 Furchgott RF The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA. 1996; 276: 1186-1188 Crossref PubMed Google Scholar In the cardiovascular system L-NMMA vasoconstricts, causes hypertension, increases platelet activation, and enhances atherogenesis. Asymmetrical dimethylarginine (ADMA) also inhibits nitric-oxide synthase and produces near-identical effects to L-NMMA. 2 Vallance P Leone A Calver A Collier J Moncada S Accumulation of an endogenous inhibitor of nitric-oxide synthesis in chronic renal failure. Lancet. 1992; 339: 572-576 Summary PubMed Scopus (1982) Google Scholar It was on this background that interest was aroused in the discovery that both L-NMMA and ADMA are naturally occurring compounds that circulate in plasma and are excreted in urine. 2 Vallance P Leone A Calver A Collier J Moncada S Accumulation of an endogenous inhibitor of nitric-oxide synthesis in chronic renal failure. Lancet. 1992; 339: 572-576 Summary PubMed Scopus (1982) Google Scholar Might these naturally occurring inhibitors contribute to pathological changes by blocking nitric-oxide generation? Risk of acute coronary events and serum concentration of asymmetrical dimethylarginineAsymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor, which has been suggested to be a novel independent risk factor for endothelial dysfunction and coronary heart disease. We investigated the association of ADMA concentration in serum with risk of acute coronary events. We did a prospective, nested, case-control study in middle-aged men from eastern Finland. In an analysis of men who did not smoke, those who were in the highest quartile for ADMA (>0·62 μmol/L) had a 3·9-fold (95% CI 1·25–12·3, p=0·02) increase in risk of acute coronary events compared with the other quartiles. Full-Text PDF Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective studyIn haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure. Full-Text PDF" @default.
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• W1989656393 date "2001-12-01" @default.
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• W1989656393 title "Importance of asymmetrical dimethylarginine in cardiovascular risk" @default.
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• W1989656393 doi "https://doi.org/10.1016/s0140-6736(01)07229-4" @default.
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