Effects of nifedipine and platelet activating factor antagonist (BN 52021) in glycerol-induced acute renal failure in rats.
We studied the actions of nifedipine and the platelet activating factor (PAF) antagonist BN 52021 on renal and tubular function in glycerol-induced acute renal failure (Gly-ARF). The tubular handling of sodium was evaluated through the lithium clearance method in awake rats in metabolic cages. The sequential analysis of tubular function 3, 6, 12, and 24 h after Gly-ARF showed a sharp decrease in fractional proximal Na reabsorption (FPRNa)--control 74.1 +/- 12.5%, 3 h: 79.5 +/- 6.0%; 6 h: 41.8 +/- 15.9%; 12 h: 22.9 +/- 17.9%; and 24 h: 31.1 +/- 16.2% (p < 0.001) while fractional distal Na reabsorption (FDRNa) did not change during the study. The effect of nifedipine (20 mg/kg p.o.) and BN 52021 (1 mg/kg i.p.) were evaluated 24 h after the induction of Gly-ARF. Both drugs attenuated the reduction in creatinine clearance (control 431.8 +/- 108.2, glycerol 96.7 +/- 43.8, glycerol plus nifedipine 264.9 +/- 103.5, and glycerol plus BN 52021 188.9 +/- 69.8 microL/min/100 g, p < 0.001). However, only nifedipine could keep FPRNa higher than untreated rats (58.3 +/- 13.2 vs. 31.1 +/- 16.2%, p < 0.05) and reduced the tubular necrosis on histologic semiquantitative analysis. Our data showed that nifedipine and BN 52021 could protect against filtration failure in Gly-ARF but that only nifedipine reduced the proximal tubular lesion.
Homsi
E
E
Faculdade de Ciências Médicas, Universidade Estaoual de Campinas, São Paulo, Brazil.
Oliveira Dias
E P
EP
Garcia
W E
WE
Gontijo
J A
JA
Figueiredo
J F
JF
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D003404:Creatinine / Q000378:metabolism* / Q000652:urine; D004195:Disease Models, Animal; D004224:Diterpenes; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D046934:Ginkgolides; D007274:Injections, Intraperitoneal; D007677:Kidney Function Tests; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D014665:Vasodilator Agents; D003404:Creatinine; C045856:ginkgolide B; D009543:Nifedipine