Thromboxane mediates the renal hemodynamic effects of platelet activating factor

J. Yoo, D. Schlondorff, J. Neugarten

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Abstract

The mechanism by which platelet-activating factor affects renal hemodynamics is controversial. In the present study we examined the hypothesis that thromboxane mediates the renal hemodynamic response to platelet activating factor (PAF) by determining the effects of pretreatment with a selective thromboxane receptor antagonist. Infusion of platelet-activating factor into the left renal artery of normal rats in a dose that failed to alter mean arterial pressure or blood hematocrit values reduced urinary flow rate from 25.9 ± 6.3 to 12.6 ± 1.5 μl/min (P < .01), reduced effective renal plasma flow rate from 14.01 ± 2.09 to 5.42 ± 2.38 ml/min/kg body weight (P < .01), reduced glomerular filtration rate from 4.81 ± 1.00 to 1.68 ± 0.34 ml/min/kg (P < .03), and increased the fractional excretion of protein from 0.021 ± 0.008 to 0.094 ± 0.005 percent (P < .05). Pretreatment with the selective thromboxane receptor antagonist SKF 96148 (10 mg/kg) not only prevented PAF-induced reductions in effective renal plasma flow rate and glomerular filtration rate but increased these values (effective renal plasma flow rate: 14.09 ± 2.76 vs. 16.84 ± 2.08 ml/min/kg, P < .05; glomerular filtration rate: 4.42 ± 0.43 vs. 5.50 ± 0.59 ml/min/kg, P < .03) and aborted proteinuria. Pretreatment with indomethacin (2 mg/kg) ameliorated PAF-induced alterations in renal hemodynamics and glomerular permselectivity in the final collection period. Infusion of lyso-PAF, a biologically inactive precursor of PAF, or of indomethacin alone or SKF 96148 alone had no significant effect on measured parameters. These observations suggest that thromboxane mediates the renal hemodynamic and permselective effects of PAF.

Original languageEnglish (US)
Pages (from-to)743-748
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number2
Publication statusPublished - Jan 1 1990

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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