Asymmetric dimethylarginine (ADMA) measurement is used in assessing the likelihood of future coronary events in patients with coronary heart disease, type II diabetes mellitus, hypercholesterolemia, or kidney disease.
More information
Dimethylarginines, asymmetric (ADMA), and symmetric (SDMA), are the methyl derivates of L-arginine, present in human blood at micromolar levels. They result from the degradation of methylated proteins during hydrolytic protein turnover.
ADMA inhibits nitric oxide (NO) synthesis via competitive inhibition of nitric oxide synthase (NOS). SDMA does not directly interfere with NOS activity but may still have an inhibitory effect on NO synthesis by suppressing cellular uptake of its precursor, L-arginine, and inhibiting renal tubular absorption of L-arginine.
NO has multiple targets in humans, including cardiovascular, nervous, and immune systems. NO is an important vasodilator that regulates systemic blood pressure. NO inhibits superoxide generation, the interaction of circulating blood elements with the vessel wall, platelets adhesion and aggregation, smooth muscle cell proliferation, and the accumulation of lipids within the vessel wall. Its deficiency results in endothelial dysfunction and atherosclerotic vascular complications. NO may also regulate apoptosis, angiogenesis, cell cycle, and metastasis of malignant cells.
Increased ADMA plasma levels are linked to endothelial dysfunction, vasoconstriction, blood pressure elevation, and the aggravation of experimental atherosclerosis. Elevated plasma ADMA concentrations have been noted in numerous clinical conditions associated with NO-dependent endothelial dysfunction, e.g., hypercholesterolemia, hypertension, myocardial infarction, chronic renal failure, chronic heart failure, diabetes mellitus, homocysteinemia, and peripheral arterial disease.
The strongest association between ADMA and all-cause mortality has been observed in critically ill patients from intensive care units (ICU). Still, statistically significant relations with all-cause mortality have also been noted in the general population, in patients with renal diseases, peripheral arterial disease, and in those with prevalent cardiovascular diseases (CVD).
ADMA and SDMA have different clearance pathways. SDMA and partially ADMA are excreted unchanged by the kidney, and some ADMA and less SDMA are subject to biliary excretion. However, the major metabolic pathway of ADMA involves its degradation by dimethylarginine dimethylaminohydrolase (DDAH) into dimethylamine (DMA) and L-citrulline (CIT). The metabolites of ADMA are excreted in the urine.
