ABSTRACT
Normal endothelial function critically depends on the bioavailability of nitric oxide (NO). NO is formed in the endothelium from L-arginine by the endothelial nitric oxide synthase (eNOS). The maintenance of endothelial function and NO production plays an important role in regulating vascular tone and structure. Furthermore, NO has anti-infl ammatory, antithrombogenic and anti-proliferative properties, which can be summarized as “anti-atherogenic” effects. The endogenously formed L-arginine derivatives NG,NG-asymmetric dimethylarginine (ADMA) and NG-monomethyl-Larginine (L-NMMA) can interfere with NO production by competitive inhibition of the enzyme, whereas NG,N’-symmetric dimethylarginine (SDMA) interferes indirectly with NO production by limiting substrate availability for the enzyme. NOS inhibition by elevated levels of endogenous L-arginine derivatives results in endothelial dysfunction, which is an early step during the development of atherosclerosis. Over the past decade, endogenous NOS inhibitors have been shown to be markers and mediators of cardiovascular disease in a number of patient populations and to be
Department of Clinical Pharmacology and Toxicology, University Medical Center HamburgEppendorf, Martinistr. 52, 20246 Hamburg. 1E-mail: m.anderssohn@uke.de 2E-mail: boeger@uke.de *Corresponding author
independent predictors of mortality both in patients as well as in the general population. This chapter will summarize the synthesis, metabolism and biological function of endogenously formed L-arginine derivatives and discuss their role in the pathophysiology of cardiovascular and metabolic disease.
