Evaluation of the efficacy of felodipine in two models of acute renal failure in dogs.
Acute renal failure was induced in pentobarbital anesthetized dogs either by withdrawal of the blood and/or by acute renal artery occlusion and efficacy of felodipine in preserving renal function was evaluated. In Wiggers' model of hemorrhagic shock, animals were allowed to bleed into a reservoir and after maintaining a hypotensive state (40-45 mm Hg) for 150 minutes, blood was reinfused and recovery in the renal function was evaluated. In a separate series, a renal artery was completely occluded for 45 minutes and after release of the occlusion recoveries in various markers of renal function were monitored. Felodipine 0.01 mumol/kg i.v. or the vehicle was administered ten minutes before hemorrhage or ten minutes prior to initiation of renal artery occlusion. Comparison of the data between the vehicle-treated dogs from the two models show that although renal blood flow (RBF) was restored to similar levels, recoveries in glomerular filtration rate (GFR), urine volume (UV), urinary excretion of sodium (UNa V) and potassium (UK V) were severely depressed in shock model (15 to 25% of the basal value) and consistently lower than the recoveries in the renal artery occlusion model (30-50%). These data could suggest that the extent of renal impairment is more severe in hemorrhagic shock. Nevertheless, felodipine pretreatment provided significant protection to renal function from ischemic damage in both the models; the drug-treated groups were characterized by significant recoveries in GFR, UNa V and UK V (60-100%) and by prompt and full restoration of RBF and UV.(ABSTRACT TRUNCATED AT 250 WORDS)
Chintala
M S
MS
Department of Pharmacology, University of Houston, Texas.
Jandhyala
B S
BS
D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015736:Felodipine / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D012078:Renal Artery Obstruction / Q000150:complications / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology
D015736:Felodipine