Protective effects of specific platelet-activating factor receptor antagonists in experimental glomerulonephritis.
The present study was undertaken to evaluate the hypothesis that enhanced production of platelet-activating factor (PAF) contributes to the renal hemodynamic alterations and impaired glomerular permselectivity that characterize the heterologous phase of nephrotoxic serum nephritis. Intravenous administration of nephrotoxic gamma globulin to normal rats led to a rapid decline in glomerular filtration rate within 60 min from 1.08 +/- 0.08 to 0.45 +/- 0.12 ml/min/100 g b.wt., P less than .001, and in effective renal plasma flow rate from 2.56 +/- 0.15 to 1.35 +/- 0.21 ml/min/100 g b.wt., P less than .02. Concomitantly, the fractional excretion of protein rose from 3.4 +/- 0.6 X 10(-5) to 11.6 +/- 2.3 X 10(-5), P less than .03. Pretreatment with the specific PAF receptor antagonists WEB 2086 or WEB 2170 significantly ameliorated the impairment in glomerular filtration rate and in effective renal plasma flow rate induced by nephrotoxic globulin. Filtration rate declined by 0.63 +/- 0.12 ml/min/100 g b.wt. 60 min after administration of nephrotoxic globulin, but fell only 0.30 +/- 0.14 ml/min/100 g b.wt. in rats pretreated with WEB 2086, P less than .05 and 0.34 +/- 0.11 ml/min/100 g b.wt. in rats pretreated with WEB 2170, P less than .01. The decline in effective renal plasma flow rate 60 min after administration of nephrotoxic globulin was 1.21 +/- 0.30 ml/min/100 g b.wt., but only 0.86 +/- 0.23 ml/min/100 g b.wt. in rats pretreated with WEB 2086, NS, and 0.52 +/- 0.21 ml/min/100 g b.wt. in rats pretreated with WEB 2170, P less than .003.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoo
J
J
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Schlondorff
D
D
Neugarten
J
J
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C063964:bepafant