Blockade of intrahepatic adenosine receptors improves urine excretion in cirrhotic rats induced by thioacetamide.

ABSTRACT

BACKGROUND/AIMS: In healthy rats, we recently showed that reduced intrahepatic portal blood flow leads to activation of hepatic adenosine receptors and a nerve-induced decrease in urine production. We hypothesize that the impaired urine excretion in liver cirrhosis is related to an increase in intrahepatic adenosine. METHODS: Anesthetized normal and thioacetamide-induced cirrhotic rats were instrumented for the measurement of urine flow, hepatic portal venous blood flow, and renal arterial blood flow. 8-Phenyltheophylline was used to block adenosine receptors. RESULTS: Compared to normal rats, cirrhotic rats had a lower baseline urine flow (P<0.05). In both normal and cirrhotic rats, intraportal but not intravenous administration of 8-phenyltheophylline increased urine flow. Saline overload in normal rats increased urine flow (from 6.8+/-0.6 to 42.2+/-4.6 microlmin(-1)) and this ability was impaired in cirrhotic rats (from 3.9+/-0.4 to 6.2+/-0.9 microlmin(-1)). Intraportal, but not intravenous, administration of 8-phenyltheophylline partially restored the renal ability to excrete the saline load. CONCLUSIONS: Impaired renal ability to excrete urine in liver cirrhosis is related to the activation of intrahepatic adenosine receptors, and this is consistent with our previous data showing renal regulation through a hepatorenal neural mechanism activated by intrahepatic adenosine.