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 increases in intraportal adenosine, which occur when the portal blood flow decreases, may trigger the hepatorenal reflex to inhibit renal water and sodium excretion. In anesthetized rats, intravenous vs. intraportal adenosine-induced effect on renal water and sodium excretion was compared in normal animals and animals with hepatic or renal denervation, and in the presence of an adenosine receptor antagonist. Compared to saline infusion, intraportal adenosine (0.02 mg kg(-1) min(-1) for 1 h) infusion decreased urine flow by 51.3% (11.7 +/- 2.3 vs. 5.7 +/- 0.5 microl min(-1)) for the first 30 min and by 49% (22.8 +/- 5.4 vs. 11.6 +/- 1.5 microl min(-1)) for the second 30-min duration. Urinary sodium excretion was also decreased. Intraportal administration of an adenosine receptor antagonist (8-phenyltheophylline (8-PT), 3 mg kg(-1) bolus injection followed by 0.05 mg kg(-1) min(-1) continuous infusion), as well as liver or kidney denervation, abolished adenosine-induced inhibition. In contrast, intravenous adenosine infusion had no influence on either urine flow or sodium excretion. The data indicated that selectively increased intraportal adenosine inhibited renal water and sodium excretion. The water and sodium retention commonly seen in the hepatorenal syndrome may be related to intraportal adenosine accumulation due to the decrease in intraportal portal flow.
Ming
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Smyth
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DD
Lautt
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D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D003714:Denervation; D007262:Infusions, Intravenous; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000294:innervation / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D014556:Urine; D014665:Vasodilator Agents / Q000494:pharmacology*; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D014665:Vasodilator Agents; D014867:Water; D012964:Sodium; D000241:Adenosine