Decreases in portal flow trigger a hepatorenal reflex to inhibit renal sodium and water excretion in rats: role of adenosine.
The regulation of renal sodium and water excretion through a hepatorenal reflex activated by the changes in hemodynamics of the portal circulation has been suggested. We hypothesize that the changes in intrahepatic blood flow and flow-related intrahepatic adenosine are involved in the control of renal water and sodium excretion by triggering a hepatorenal reflex. Anesthetized rats were instrumented to monitor the systemic, hepatic, and renal circulation. A vascular shunt connecting the portal vein and central vena cava was established to allow for control of the portal venous blood flow (PVBF). Urine was collected from the bladder. The effects of decreased PVBF on renal water and sodium excretion were compared in normal and hepatic denervated rats. Decreasing intrahepatic PVBF by half for 30 minutes decreased urine flow by 38% (12.1 +/- 1.1 vs. 7.5 +/- 0.7 microL. min(-1)) and urine sodium excretion by 44% (1.11 +/- 0.30 vs. 0.62 +/- 0.17 micromol. min(-1)). Renal arterial blood flow (RABF) and creatinine clearance were also reduced by the decreases in intrahepatic PVBF. Hepatic denervation, or intrahepatic administration of an adenosine receptor antagonist, 8-phenyltheophylline (8-PT), abolished the effects of decreasing PVBF on urine flow and sodium excretion. The data suggest that the decrease in intrahepatic PVBF triggers a hepatorenal reflex through the activation of adenosine receptors within the liver, thereby inhibiting renal water and sodium excretion. The water and sodium retention commonly seen in the hepatorenal syndrome may be related to intrahepatic adenosine accumulation resulting from the associated decrease in intrahepatic portal flow.
Ming
Zhi
Z
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Smyth
Donald D
DD
Lautt
W Wayne
WW
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure; D003714:Denervation; D004231:Diuresis; D006530:Hepatorenal Syndrome; D007668:Kidney / Q000098:blood supply / Q000294:innervation / Q000502:physiology*; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000294:innervation* / Q000502:physiology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000502:physiology / Q000601:surgery; D009318:Natriuresis; D011167:Portacaval Shunt, Surgical; D011168:Portal System / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology; D012077:Renal Artery / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine