Role of Nitric Oxide,Asymmetric Dimethylarginine and Endothelial Dysfunction in Arteriovenous Fistula Failure: Should We be More Hopeful with Nebivolol?

Abstract

Native arteriovenous (AV) fistula is the preferred form of permanent dialysis access. Despite its advantages over grafts and catheters, early and late fistula failures are relatively common and represent an enormous burden on patients and the health care system. AV fistula maturation is a complex process that has not yet been fully clarified. However, recent experimental and clinical trials showed that nitric oxide (NO) plays a crucial role in fistula maturation and maintenance. After creation of AV fistula, both vein and artery of the anastomosis need to dilate to reduce increased shear stress back to normal levels. This task is achieved mainly by NO-induced smooth muscle relaxation. Asymmetric dimethylarginine (ADMA), now considered a new uremic toxin, is a naturally occurring aminoacid that inhibits nitric oxide synthase enzyme. The endothelial NOS isoenzyme form of this enzyme is primarily responsible for generation of nitric oxide. Chronic kidney disease patients have extensive endothelial dysfunction and increased ADMA 1 levels, and consequently have diminished NO reserves. Nebivolol is a third generation, highly cardio-selective beta-blocker whose main mechanism of action is dilatation of vascular smooth muscle. This dilatation takes place by means of increased NO. We review roles of NO and ADMA in fistula maturation and hypothesize that nebivolol as a direct facilitator of NO production would be beneficial in the process of fistula maturation and maintenance of access patency.