ADMA and NOS regulation in chronic renal disease: beyond the old rivalry for l-arginine

Chronic kidney disease is associated with increased levels of assymetric NG,NG-dimethylarginine (ADMA), which is predictive of increased mortality and cardiovascular disease. ADMA induces endothelial dysfunction through competitive inhibition of the endothelial nitric oxide (eNOS) substrate L-arginine. Kajimoto et al. show that ADMA may also reduce nitric oxide production via decreased eNOS phosphorylation; this effect is mediated by the MAPK pathway and can be reversed in vivo by increased catabolism of ADMA through dimethylarginine dimethylaminohydrolase-1 overexpression.