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Although there is considerable evidence that vasodilator prostaglandins such as prostaglandin E2 (PGE2) modulate renal hemodynamics in liver cirrhosis, the role of the vasoconstrictor thromboxane A2 (TXA2) is controversial. We measured renal hemodynamics and glomerular eicosanold production in cirrhotic and control rats. Renal plasma flow, as estimated by para-aminohippurate clearance (CPAH) and glomerular filtration rate, as determined by inulin clearance (CIN), were comparable between groups; glomerular production of PGE2 and TXA2 (estimated by the metabolite thromboxane B2 [TXB2]) was slightly but not significantly higher in cirrhotic than in control rats (PGE2:1060 ± 142 pg/mg glomerular protein vs 854 ± 288 pg/mg glomerular protein; TXB2: 782 ± 103 pg/mg glomerular protein vs 468 ± 104 pg/mg glomerular protein). Addition of serum from cirrhotic rats to the incubation media failed to increase eicosanold production in glomeruli obtained from either cirrhotic or control rats. Cyclooxygenase inhibition with 5 mg/kg indomethacin, a dose sufficient to result in a 68% inhibition of glomerular PGE2 synthesis, decreased both CPAH (from 6.59 ± 0.69 ml/min to 4.52 ± 0.67 ml/min, p< 0.05) and CIN (from 1.34 ± 0.16 ml/min to 0.68 ± 0.07 ml/min, p < 0.01) in cirrhotic rats. Thromboxane synthesis inhibition with 1 mg/kg UK-38485, which resulted in an 84% decrease in glomerular TXB2, did not significantly affect either CPAH or CIN; however, there was a strong trend toward improvement in CIN (from 1.23 ± 0.11 ml/mln to 1.43 ± 0.15 ml/min (0.05 < p < 0.1). Neither drug affected renal hemodynamics in control rats. Our results suggest that, although thromboxane may play a role in the regulation of glomerular filtration rate, the predominant effect of cyclooxygenase products in cirrhosis is to maintain renal hemodynamics.
Abbreviations:CIN = inulin clearance (), CPAH = para-aminohippurate clearance (), EBSS = Earle's balanced salt solution (), EDTA = ethylenediaminetetraacetic acid (), HEPES = N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (), PAH = para-aminohippurate (), PBS = phosphate-buffered saline solution (), PGE2 = prostaglandin E2 (), TXA2 = thromboxane A2 (), TXB2 = thromboxane B2 ()
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Accepted: November 7, 1988
Received in revised form: October 31, 1988
Received: January 13, 1988
☆Supported by grants from the Veterans Administration (Research Advisory Group and Merit Review) and from Loyola University Stritch School of Medicine (Biomedical Research Support Grant).
☆☆Presented in preliminary form at the American Society of Nephrology Annual Meeting, December 1987.
© 1989 Published by Elsevier Inc.