Increased activity of guanosine 3 '-5 '-cyclic monophosphate phosphodiesterase in the renal tissue of cirrhotic rats with ascites

A possible defect of guanosine 3'-5'-cyclic monophosphate (cGMP) content in the renal tissue caused by an increased activity of cGMP phosphodiesterase (PDE) has, so far, not been evaluated in the pathogenesis of renal resista nce to endogenous natriuretic peptides (ENP) in cirrhosis with ascites, To rest this hypothesis the activity of cGMP-PDE and the concentration of cGMP were evaluated in vitro in the renal tissue of 10 control rats and 10 cirr hotic rats with ascites before and after the intravenous (IV) administratio n of Zaprinast (Sigma, St. Louis, MO), a specific cGMP-PDE inhibitor (30 mu g/kg/min), Moreover, the effects of the intravenous administration of Zapr inast (15 mu g/kg/min and 30 mu g/kg/min) on renal plasma flow (RPF), glome rular filtration rate (GFR), and urinary sodium excretion (UNaV) were evalu ated in 10 conscious control rats and 10 conscious cirrhotic rats with asci tes, The effects of Zaprinast on plasma renin activity (PRA) was also evalu ated in 10 control rats and in 10 cirrhotic rats with ascites. Finally, the effect of Zaprinast on RPF, GFR, and UNaV were evaluated in 10 cirrhotic r ats after the IV administration of the ENP-receptor antagonist, HS-142-1. T he renal content of cGMP was reduced in cirrhotic rats because of increased activity of cGMP-PDE. Zaprinast inhibited cGMP-PDE activity and increased the renal content of cGMP in these animals. The inhibition of cGMP-PDE was associated with an increase in RPF, GFR, and UNaV and a reduction in PRA. H S-142-1 prevented any renal effect of Zaprinast in cirrhotic rats. In concl usion, an increased activity of the cGMP-PDE in renal tissue contributes to the renal resistance to ENP in cirrhosis with ascites.