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We have developed a model of endotoxemic acute renal failure in the anesthetized male rat in which acute endotoxin infusion induces renal vasoconstriction and decreased glomerular filtration rate (GFR) in the absence of systemic hypotension. Because increased levels of platelet activating factor (PAF) have been observed in experimental models of endotoxemia, we pretreated rats with PAF receptor antagonist BN 52021 or SRI 63-675 before administering endotoxin. Compared with treatment with vehicle, treatment with BN 52021 led to significant preservation of RBF, GFR, and urine flow rate. Pretreatment with SRI 63-675 resulted in significant improvement in RBF while completely preventing the fall in GFR and urine flow rate. Intrarenal artery infusion of exogenous PAF (30 ng/kg/min) resulted in renal vasoconstriction, decreased GFR, and oliguria. These effects were also prevented by pretreatment with SRI 63-675. Thus, the adverse renal hemodynamic effects of endotoxemia were blunted or prevented by pretreatment with PAF receptor antagonists. We conclude that endogenously produced PAF is an important mediator of endotoxemic acute renal failure.
Abbreviations:BSA = bovine serum albumin (), GFR = glomerular filtration rate (), LPS = lipopolysaccharides (), MAP = mean arterial pressure (), PAF = platelet activating factor (), PLA2 = phospholipase A2 (), RBF = renal blood flow (), RPF = renal plasma flow ()
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Accepted: November 7, 1988
Received in revised form: October 20, 1988
Received: June 21, 1988
☆Supported by funds from the Veterans Administration.
☆☆Presented in part at the 1987 midwestern meeting of the American Federation of Clinical Research, held in Chicago, and at the 1987 national meeting of the American Society of Nephrology, held in Washington, D.C.
© 1989 Published by Elsevier Inc.