Asymmetric dimethylarginine, derangements of the endothelial nitric oxide synthase pathway, and cardiovascular diseases.

摘要: Analogues of L-arginine that are chemically modified at the terminal guanidino nitrogen group, such as Nomega-monomethy-L-arginine (L-NMMA), have been used for nitric oxide synthase inhibition. However, L-NMMA and other methylated analogues also endogenously formed. Among these, asymmetric dimethylarginine (ADMA) symmetric (SDMA) shown to be most abundant. Like L-NMMA, ADMA is an inhibitor NO synthase, whereas SDMA inactive. synthesized by N-methyltransferases, a family enzymes methylate residues within specific proteins. Free released during proteolytic cleavage proteins; it can detected in plasma urine, but its intracellular concentrations appear much higher. metabolized enzyme dimethylaminohydrolase (DDAH), inhibition DDAH activity has lead increased levels endothelial dysfunction. Plasma elevated endstage renal failure, atherosclerosis hypercholesterolemia, hypertension, heart failure. Although molecular cause elevation concentration these diseases not fully elucidated, evidence accumulating one dysfunction diseases. Moreover, may marker or even risk factor cardiovascular disease. Therefore, pharmacological modulation novel therapeutic target