Improvement of Postischemic Acute Renal Failure with the Novel Orally Active Endothelin-A Receptor Antagonist LU 135252 in the Rat

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Abstract
The endothelin (ET) system may play an important role in the pathogenesis of acute renal failure (ARF). We hypothesize that the course of ARF in an ischemia-reperfusion model will be markedly attenuated by the orally active ETA-receptor antagonist LU 135252 (LU) because of an improvement of renal perfusion. ARF was induced in rats by clamping both renal arteries for 60 min. The study was divided into two parts. In part 1, Rats received LU orally (100 mg/kg/day) starting 1 h after induction of ARF for 14 days. Crs, Clcr and FEna were measured on days 1, 6, 9, and 14 after ARF. Crs was lower in the treatment group on days 1 [1.3 ± 0.31 mg/dl (n = 9) vs. 2.7 ± 0.46 mg/dl (n = 10); p cr