Asymmetric dimethylarginine (ADMA) : an endogenous inhibitor of nitric oxide synthase and a novel cardiovascular risk molecule

Asymmetric dimethylarginine (ADMA), a methyl derivate of the amino acid arginine, is produced by the physiological degradation of methylated proteins. ADMA is the major endogenous inhibitor of nitric oxide synthase (NOS), the enzyme which synthesizes nitric oxide (NO), a molecule endowed with important anti-atherosclerotic properties. Increased plasma ADMA concentrations cause impaired NO synthesis leading to endothelial dysfunction and atherosclerotic vascular disease. Increased plasma ADMA levels mainly occur following inhibition of the enzyme responsible for ADMA catabolism, dimethylarginine dimethylaminohydrolase (DDAH), by oxidative stress triggered by several cardiovascular risk factors. This paper reviews the effects on cardiovascular function produced by ADMA administration to experimental animals and humans. In addition, a number of clinical conditions associated with increased plasma ADMA concentrations are considered. Then the growing body of literature indicating that plasma ADMA levels have a predictive value for major cardiovascular events in prospective studies is discussed. Finally, an analysis is provided of the published data concerning the possibility to modulate plasma ADMA levels using drugs belonging to different pharmacological classes.