Platelet-activating factor mediates endotoxin-induced acute renal insufficiency in rats.
Platelet-activating factor (PAF) may contribute to the renal functional impairment of endotoxemia. We therefore examined 1) the effects of two specific PAF-receptor antagonists, L-653,150 and L-652,731, on endotoxin-induced acute renal insufficiency and 2) the renal hemodynamic actions of PAF in anesthetized postpartum Wistar rats. An intravenous injection of endotoxin at 150 micrograms/kg reduced glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) without a change in mean arterial pressure. L-653,150, 50 mg/kg orally, attenuated the endotoxin-induced fall in GFR, RPF, and FF. An intravenous injection of L-652,731, 0.3 mg/kg, followed by an infusion at 16 micrograms.kg-1. min-1 prevented the endotoxin-elicited reduction in GFR, RPF, and FF. L-652,731 also reversed the endotoxin-induced renal functional impairment. PAF, infused at 16 ng.kg-1.min-1 into the suprarenal aorta, reduced GFR, RPF, and FF without a significant change in renal arterial pressure. L-652,731 prevented the PAF-induced changes. In contrast, meclofenamate worsened the renal hemodynamic effects of PAF. We conclude that PAF may play an important role in mediating the endotoxin-induced acute hemodynamic renal insufficiency in rats with normotensive endotoxemia.
Wang
J
J
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Dunn
M J
MJ
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D004731:Endotoxins; D005260:Female; D005663:Furans / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D012039:Regional Blood Flow; D013876:Thiophenes / Q000494:pharmacology
D004731:Endotoxins; D005663:Furans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013876:Thiophenes; C039351:platelet activating factor receptor; C050450:L 653150; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran