Effect of Rosiglitazone on ADMA in Critical Illness

Endothelial vasodilatation dysfunction precedes the development of arteriosclerosis. The endothelium plays a pivotal role in the control of the vascular tone by releasing nitric oxide (NO). The amino acid arginine is the sole substrate for the enzyme NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous derivative of arginine that inhibits NOS. Thus the arginine/ADMA ratio an important determinant of NO production by NOS. ADMA is an independent risk factor for cardiovascular disease, but elevated levels of ADMA have also been shown to be a strong independent predictor of ICU mortality. The central mechanism by which ADMA may cause deterioration in critically ill patients is by impairing organ blood flow and reducing cardiac function, especially during stress. Accumulation of ADMA could thereby be a causative factor in the development multi organ failure (MOF). Thus inhibition of NO production by ADMA may become especially important when cardiac demand is increased.