Platelet-activating factor antagonists treatment protects against postischemic acute renal failure in rats.
Platelet-activating factor (PAF-acether) has been shown to be produced by the kidney and to sharply reduce glomerular filtration rate (GFR) and renal plasma flow (RPF). Thus, PAF-acether could be a possible mediator of the reduction of GFR and RPF in ischemic-induced acute renal failure (ARF). We have assayed the effect of inhibiting the interaction of PAF-acether with its receptor using two specific PAF-acether antagonists, BN-52021 and alprazolam, on the evolution of the GFR and RPF, in the experimental model of ARF induced in rats by clamping the left artery for 60 min. In addition, we have measured arteriovenous differences in PAF-acether concentration, as well as PAF-acether content in glomeruli from rats with ARF pretreated or not with BN-52021. In metabolic cage studies, plasma creatinine increased more in the untreated than in the BN-52021-treated group, whereas creatinine clearance was higher in treated than in untreated rats. In acute clearance experiments, after renal artery clamping, untreated rats showed a marked oliguria and reduction of the inulin clearance (greater than 99%), which showed no recovery 90 min after clamp release, whereas GFR reached values above 0.1 ml/min in the rats treated with BN-52021 or alprazolam, with clearly significant statistical differences. Results of p-aminohippurate clearance were similar to those of GFR. Glomeruli from rats with ARF had greater amounts of PAF-acether than glomeruli from normal rats, whereas glomeruli from BN-52021-treated rats with ARF produced intermediate amounts. These results provide evidence for a role for PAF-acether in the genesis of this model of experimental ARF.
López-Farré
A
A
Laboratory of Renal Physiopathology, Fundación Jiménez Diaz-CSIC, Madrid, Spain.
Bernabeu
F
F
Gómez-Garre
D
D
Ramon y Cajal
S
S
Braquet
P
P
López-Novoa
J M
JM
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D004224:Diterpenes; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B; D000525:Alprazolam