Platelet-activating factor mediates glycerol-induced acute renal failure in rats.
1. We have studied the effect of inhibiting the interaction of platelet-activating factor with its receptor by using two structurally different antagonists BN-52021 (1 mg/kg, intraperitoneally) and alprazolam (1 and 5 mg/kg, intraperitoneally) on the evolution of glomerular filtration and renal blood flow, in the experimental model of acute renal failure induced by the intramuscular injection of glycerol in rats. 2. We have also measured arteriovenous differences in platelet-activating factor concentration, as well as platelet-activating factor content in glomeruli from rats with glycerol-induced acute renal failure. 3. After glycerol injection, untreated rats showed a marked reduction in inulin clearance which reached 77% in the first 30 min. The reduction was only 27% in the rats treated with BN-52021 and 38% in the rats treated with alprazolam (5 mg/kg), with statistically significant differences between treated and untreated groups. 4. Clearance of p-aminohippuric acid was also improved with BN-52021 or alprazolam treatment. 5. This protective effect of BN-52021 was observed in a more prolonged follow-up (3 days). 6. Glomeruli from rats with acute renal failure, treated or untreated with BN-52021, showed similar amounts of platelet-activating factor, whereas it was undetectable in glomeruli from normal rats. Furthermore, rats with glycerol-induced acute renal failure released greater amounts of platelet-activating factor. 7. These results provide evidence of a role for platelet-activating factor in the genesis of this model of experimental acute renal failure.
López-Farré
A
A
Medical Research Institute, Fundación Jiménez Diaz-CSIC, Madrid, Spain.
Gómez-Garre
D
D
Bernabeu
F
F
Ramón y Cajal
S
S
Perez-Rodrigo
P
P
Braquet
P
P
López-Novoa
J M
JM
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005990:Glycerol; D007668:Kidney / Q000098:blood supply; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010936:Plant Extracts; D010972:Platelet Activating Factor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B; D005990:Glycerol; D000525:Alprazolam