Importance of renal prostaglandins in control of renal function after chronic ligation of the common bile duct in dogs.
To explore the possible vasoregulatory role of renal prostaglandins during liver disease, excretory rates of PGE2, PGF2 alpha, and a metabolite of PGI2, 6k-PGF1 alpha, were determined before and after chronic ligation of the common bile duct in 23 dogs. Bile duct ligation for 50 +/- 3.7 days (mean +/- SEM) significantly increased serum bilirubin and alkaline phosphatase. PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were significantly (p less than 0.01) increased following chronic bile duct ligation, by approximately 100%, 80%, and 500%, respectively, with similar increments in both ascitic and nonascitic animals. In 10 sham-ligated animals, PGE2, PGF2 alpha, and 6k-PGF1 alpha excretion rates were unchanged. In 6 dogs sequential measurements of urine prostaglandins indicated that PGE2 and 6k-PGF1 alpha excretion were significantly increased at 2, 4, and 6 weeks after ligation, whereas the increase in PGF2 alpha excretion was not significant until 6 weeks. Indomethacin (2 mg/kg) reduced prostaglandin excretion by 65% to 90% and significantly increased arterial pressure, decreased glomerular filtration rate and renal blood flow, and increased renal vascular resistance from 0.53 +/- 0.09 to 0.90 +/- 0.13 mm Hg/ml/min. Fractional renal blood flow, assessed by microspheres, was disproportionately reduced in the inner cortex after prostaglandin inhibition in the chronic bile duct ligation group. Indomethacin did not significantly alter renal function in sham animals, despite comparable reductions in prostaglandin excretion. These data demonstrate that, in dogs with experimental liver disease produced by chronic bile duct ligation, renal prostaglandin synthesis is increased, and the enhanced synthesis of vasodilatory prostaglandins serves to maintain renal blood flow and glomerular filtration rate.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D002908:Chronic Disease; D003135:Common Bile Duct / Q000502:physiology; D004285:Dogs; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008107:Liver Diseases / Q000378:metabolism*; D011453:Prostaglandins / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine; D011460:Prostaglandins F / Q000652:urine
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D015121:6-Ketoprostaglandin F1 alpha