Effect of zaprinast on nitric oxide levels in serum and aortic tissue.

Nitric oxide (NO), which is synthesized from the guanidino nitrogen of l-arginine by nitric oxide synthase (NOS), plays an important role in many physiological and pathological processes. Most of the effects of NO are mediated by cyclic guanosine 3'5 monophosphate (cGMP), which is synthesized by soluble guanylate cyclase (sGC) and degraded by phosphodiesterases (PDEs). Although the NO/cGMP pathway has been extensively studied, remarkably little is known about the regulation of NO release. Furthermore, controversial studies have indicated that intervention of the sGC/cGMP pathway modulates the release of NO. The purpose of this study was to evaluate the hypothesis that drugs that affect the sGC/cGMP pathway may modulate NO release and, if so, is there a correlation between NO levels and blood pressure effect? To this end, we investigated the effects of the PDE 5 inhibitor zaprinast on mean arterial pressure (MAP), nitrite/nitrate levels and cGMP in normotensive male Sprague Dawley rats. The results of the current study indicated that zaprinast dose-dependently increased plasma cGMP levels at 18, 24 and 36 mg/kg and decreased MAP at 24 and 36 mg/kg. However, zaprinast at 18, 24 and 36 mg/kg did not affect NO levels either in serum or aortic tissue. We have concluded that the PDE 5 inhibitor zaprinast has no regulatory effect on NO release in serum and aortic tissue, and NO was not involved in the hypotensive effect of zaprinast. (c) 2004 Prous Science. All rights reserved.