Thromboxane mediates the renal hemodynamic effects of platelet activating factor.
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 microliters/min (P less than .01), reduced effective renal plasma flow rate from 14.01 +/- 2.09 to 5.42 +/- 2.38 ml/min/kg body weight (P less than .01), reduced glomerular filtration rate from 4.81 +/- 1.00 to 1.68 +/- 0.34 ml/min/kg (P less than .03), and increased the fractional excretion of protein from 0.021 +/- 0.008 to 0.094 +/- 0.005 percent (P less than .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 less than .05; glomerular filtration rate: 4.42 +/- 0.43 vs. 5.50 +/- 0.59 ml/min/kg, P less than .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.
Yoo
J
J
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Schlondorff
D
D
Neugarten
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017482:Receptors, Thromboxane; D012079:Renal Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism* / Q000494:pharmacology
D010648:Phenylacetates; D010972:Platelet Activating Factor; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013929:Thromboxane B2; C051762:daltroban; D007213:Indomethacin