One of the earliest manifestations of endothelial dysfunction is nitric oxide (NO) deficiency, which promotes atherosclerosis. ADMA (asymmetric dimethylarginine) and SDMA (symmetric dimethylarginine), its structural isomer, are metabolites of L-arginine, an amino acid that is catalyzed to L-citrulline and NO by nitric oxide synthase (NOS). Both ADMA and SDMA have distinct pathophysiologies and manifestations. ADMA is a competitive inhibitor of NOS thereby reducing NO production and promoting endothelial dysfunction. SDMA also interferes with NO production, but does so indirectly by reducing the cellular availability of arginine. ADMA is primarily cleared through enzymatic degradation in the bloodstream and identifies subclinical cardiovascular disease. Conversely, SDMA is primarily excreted in the urine and identifies reduced renal function.
ADMA is a metabolite of L-arginine and can inhibit NO production. Elevated levels of ADMA are associated with endothelial dysfunction, insulin resistance, hypertension and subclinical atherosclerosis.