Effect of Endothelin-A Receptor Blockade on the Early Phase of Ischemia/Reperfusion-Induced Acute Renal Failure in Anesthetized Rats

Abstract

Background: Previous studies have shown increases in endothelin (ET) concentration of plasma and renal tissues in acute renal failure (ARF). ET has a potent vasoconstrictor effect, through binding with its ETA receptors, and may play some roles in renal hemodynamic dysfunction in ARF.Objective: To examine the beneficial effect of a selective ETA-receptor antagonist on renal dysfunction and tissue damage occurring during the early phase of ischemia/reperfusion-induced ARF.Methods: Pentobarbital anesthetized rats were prepared for the measurement of blood pressure and renal function. A 0.5 hr clearance period was taken as control period, followed by 1 hr, and then a 4 hr experimental clearance period was taken. In ischemia/reperfusion (I/R) group, 30 min after the end of the control clearance period, renal ischemia was induced by bilateral renal artery clamping for 30 min. In drug-treated (I/R+D) group, a selective ETA-receptor antagonist (UK-350,926) was infused iv at 50 mg/kg/min for 30 min before and 2 hr following occlusion of renal arteries. There was also a sham-operated group.Results: In I/R group, renal ischemia lowered creatinine clearance (CCr) by 76% (p<0.001), but elevated urine flow rate (V­0) by 2.9-fold (p<0.01) and absolute Na+excretion (UNaV0) by 3.2-fold (p<0.05) during the 4 hr reperfusion period as compared to their own control values. In I/R+D group, V0 and UNaV0 did not change significantly during the 4 hr experimental period, but the amount of decrease in CCr was equal to that of I/R group. Histological examination showed a mild degree of tissue damage in the cortex of I/R group but not in I/R+D and sham groups.Conclusion: Administration of the ETA-receptor antagonist does not prevent the fall of glomerular filtration, but it does ameliorate the damage of renal tissue and tubular reabsorption of Na­+ and water during 4 hrs of reperfusion following the ischemic challenge.