Key result
Rolipram infusion increases sodium and phosphate excretion in cirrhotic rats with ascites.
Why the study?
Does intravenous administration of rolipram improve sodium excretion in cirrhotic rats with ascites?
Does intravenous administration of rolipram improve sodium excretion in cirrhotic rats with ascites?
p-value: p=< 0.05
Inhibition of cAMP-PDE4 with rolipram improves sodium excretion in cirrhotic rats with ascites, suggesting increased renal cAMP-PDE activity contributes to sodium retention in this condition.
No immediate clinical role for rolipram in ascites; leaves open PDE4 inhibition as a target for human translation.
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. CONCLUSION: 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.
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Ahloulay et al. (2005) studied Cirrhosis and ascites. cAMP and rolipram vs. Control rats and non-ascitic cirrhotic rats was evaluated on Sodium and phosphate excretion and cAMP-PDE activity (p=< 0.05). Rolipram infusion significantly increased sodium and phosphate excretion in cirrhotic rats with ascites, while cAMP-PDE activity was higher in ascitic than control rats (P < 0.05).
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