Intrahepatic adenosine triggers a hepatorenal reflex to regulate renal sodium and water excretion

The mechanism for water and sodium retention in liver cirrhosis is related to the disturbance in hepatic portal circulation. We hypothesize that the i ncreases in intraportal adenosine, which occur when the portal blood flow d ecreases, may trigger the hepatorenal reflex to inhibit renal water and sod ium excretion. In anesthetized rats, intravenous vs. intraportal adenosine- induced effect on renal water and sodium excretion was compared in normal a nimals and animals with hepatic or renal denervation, and in the presence o f an adenosine receptor antagonist. Compared to saline infusion, intraporta l adenosine (0.02 mg kg(-1) min(-1) for I h) infusion decreased urine flow by 51.3% (11.7 +/- 2.3 vs. 5.7 +/- 0.5 mul min(-1)) for the first 30 min an d by 49% (22.8 +/- 5.4 vs. 11.6 +/- 1.5 mul min(-1)) for the second 30-min duration. Urinary sodium excretion was also decreased. Intraportal administ ration of an adenosine receptor antagonist (8-phenyltheophyl-line (8-PT), 3 mg kg(-1) bolus injection followed by 0.05 mg kg(-1) min(-1) continuous in fusion), as well as liver or kidney denervation, abolished adenosine-induce d inhibition. In contrast, intravenous adenosine infusion had no influence on either urine flow or sodium excretion. The data indicated that selective ly increased intraportal adenosine inhibited renal water and sodium excreti on. The water and sodium retention commonly seen in the hepatorenal syndrom e may be related to intraportal adenosine accumulation due to the decrease in intraportal portal flow. (C) 2001 Elsevier Science B.V.All rights reserv ed.