Renal perfusion in dogs with experimental hepatic cirrhosis: role of prostaglandins.
Increased renal production of prostaglandins are thought to be important for the maintenance of kidney blood flow in advanced cirrhosis. In alert, unanesthetized dogs with chronic cirrhosis and ascites, produced by bile duct ligation, we measured inulin and p-aminohippurate (PAH) clearance before and after the intravenous administration of 2 mg/kg indomethacin, an inhibitor of prostaglandin production. Inulin and PAH clearance declined by 42 and 43%, respectively. This decline in renal perfusion was not associated with changes in blood pressure or cardiac output. If portal hypertension was prevented by creating an end-side portacaval anastomosis at the time of bile duct ligation, indomethacin was without effect on renal perfusion whether or not the dog had ascites. If ascites was completely mobilized in cirrhotic dogs with portal venous hypertension with the aid of a LeVeen valve, indomethacin depressed inulin and PAH clearance as usual during the steady-state period once all ascites had been removed. An attempt was made to determine some of the factors mediating the apparent increase in renal prostaglandin synthesis by administering various pharmacological antagonists. The inhibition of angiotensin effect with saralasin and the inhibition of kallikrein with aprotinin prevented the usual indomethacin effect. It is concluded that portal hypertension, but not a "sick liver per se, in cirrhosis activates the renin-angiotensin system to both produce renal vasoconstriction and stimulate prostaglandin synthesis, thereby normalizing renal perfusion. Renal kallikrein also appears to play a role, probably by augmenting renin release.
D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D002763:Cholecystectomy; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D010130:p-Aminohippuric Acid
D007093:Imidazoles; D011453:Prostaglandins; C029899:imidazole; D002216:Captopril; D011433:Propranolol; D012504:Saralasin; D007213:Indomethacin; D010130:p-Aminohippuric Acid; D010646:Phentolamine