title: Cyclic AMP-phosphodiesterases inhibitor improves sodium excretion in rats with cirrhosis and ascites.
abstract: 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.
authors.affiliation: Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hôpital Beaujon, 92118 Clichy, France.
authors.forename: Mina
authors.initials: M
authors.lastname: Ahloulay
authors.forename: Lise
authors.initials: L
authors.lastname: Bankir
authors.forename: Claire
authors.initials: C
authors.lastname: Lugnier
authors.forename: Alain
authors.initials: A
authors.lastname: Le Bec
authors.forename: Odile
authors.initials: O
authors.lastname: Poirel
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
mesh_terms: 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
chemical_list: D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D020889:Rolipram