P. Angeli et al., Increased activity of guanosine 3 '-5 '-cyclic monophosphate phosphodiesterase in the renal tissue of cirrhotic rats with ascites, HEPATOLOGY, 31(2), 2000, pp. 304-310
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.