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

• Published in: Kidney international Vol. 81; no. 8; p. 722
• Main Author: Dobrian, Anca D
• Format: Journal Article
• Language: English
• Published: United States 01-04-2012
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - blood; Humans; Male; Nitric Oxide Synthase Type III - antagonists & inhibitors; Renal Insufficiency, Chronic - physiopathology
• ISSN: 1523-1755
• DOI: 10.1038/ki.2011.496

Chronic kidney disease is associated with increased levels of assymetric N(G),N(G)-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.