effect of endothelin-a receptor blockade on the early phase of ischemia/reperfusion-induced acute renal failure in anesthetized rats

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 et a receptors, and may play some roles in renal hemodynamic dysfunction in arf. objective: to examine the beneficial effect of a selective et a -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 et a -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 (c cr ) by 76% (p<0.001), but elevated urine flow rate (v­ 0 ) by 2.9-fold (p<0.01) and absolute na + excretion (u na v 0 ) 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, v 0 and u na v 0 did not change significantly during the 4 hr experimental period, but the amount of decrease in c cr 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 et a -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.