Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease.
Renal function is known to be abnormal in patients with cirrhosis. Diminished cortical blood flow due to active renal vasoconstriction is present. Renal prostaglandins, potent vasodilators, could be released by the kidney in an attempt to maintain renal blood flow. This possibility was investigated by measuring the effect of indomethacin, an inhibitor of prostaglandin synthetase, in patients with alcoholic liver disease. Administration of indomethacin reduced the effective renal plasma flow (ERPF) and creatinine clearance by 23% and 19%, respectively (P less than 0.001), and increased serum creatinine by 29% (P less than 0.001). The response to indomethacin was variable (fall in ERPF (+)7.8% to (-)67%), but was greatest in patients with ascites. Eighty percent of ascitic patients had a greater than 15% fall in ERPF after administration of indomethacin compared with 20% of nonascitic patients (P less than 0.025). An infusion of prostaglandin A1 in 13 patients corrected the decrease in ERPF and creatinine clearance that had followed the administration of indomethacin. The administration of indomethacin caused a significant fall in plasma renin activity, 8.2 +/- 2.5 to 3.6 +/- 1.4 ng/ml/hr (P less than 0.025). The fall in plasma renin activity occurred when ERPF was depressed maximally, suggesting that endogenous prostaglandins exert more control over renin release than does ERPF. Prostaglandins appear to be an important factor in maintaining renal blood flow in patients with cirrhosis and sodium retention.
D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D007677:Kidney Function Tests; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011455:Prostaglandins A, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism / Q000502:physiology; D011674:Pulse / Q000187:drug effects; D012083:Renin / Q000097:blood*
D011455:Prostaglandins A, Synthetic; D011458:Prostaglandins E; D003404:Creatinine; D012083:Renin; D007213:Indomethacin