Cyclic AMP-phosphodiesterases inhibitor improves sodium excretion in rats with cirrhosis and ascites.
BACKGROUND
The mechanisms responsible for renal dysfunction and sodium retention in cirrhosis remain unclear. Cyclic AMP (cAMP) regulates sodium reabsorption in the proximal nephron. This study investigates the role of cAMP metabolism in renal dysfunction in cirrhosis.


METHODS
Renal function was studied by the clearance technique in anesthetized control and cirrhotic rats with or without ascites. cAMP phosphodiesterase (PDE) activity was measured in the renal cortex in vitro. Moroever, the effects on renal function of the intravenous administration of cAMP and rolipram, a powerful and specific cAMP-PDE4 inhibitor, were evaluated.


RESULTS
In control and in non-ascitic cirrhotic rats, cAMP administration significantly increased sodium and phosphate excretions, but did not change these excretions in cirrhotic rats with ascites. cAMP-PDE activity was higher in ascitic than in control rats (P < 0.05). Rolipram infusion significantly increased sodium and phosphate excretion only in cirrhotic rats with ascites.


CONCLUSIONS
These results suggest that increased renal cAMP-PDE activity is responsible for resistance to the natriuretic effects of cAMP in cirrhosis and plays a role in the development of ascites.
Ahloulay
Mina
M
Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hôpital Beaujon, 92118 Clichy, France.
Bankir
Lise
L
Lugnier
Claire
C
Le Bec
Alain
A
Poirel
Odile
O
Moreau
Richard
R
Lebrec
Didier
D
D000704:Analysis of Variance; D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020889:Rolipram / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D020889:Rolipram