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Introduction & Objective: Previous studies have shown increased ET concentrations in plasma and renal tissues in ischemic or toxic acute renal failure (ARF). These increments were parallel to a reduction of renal blood flow and progression of renal dysfunction. The present study was undertaken to investigate the potential beneficial effect of the novel selective ETA antagonist (UK-350,926), on tissue damages occurring during the early phase of ischemia-reperfusion induced ARF. Materials & Methods: In pentobarbital (60 mg/kg, I.P) anaesthetized male Charles River rats’ (290-340 g) abdomens were opened via a mid abdominal incision. The urinary bladder was cannulated and renal arteries and veins of both kidneys were carefully cleared. After 2h rest, a 0.5 h clearance period was taken for basal levels, followed by two 30 min periods, and then a 4h experimental clearance period was considered. Finally, both kidneys were removed and fixed in paraffin for histological studies. The rats were divided into three groups (n=6): 1) Sham Group, 2) Ischemia/reperfusion Group (I/R), in which 30 min after the end of control clearance period, renal ischemia was induced by bilateral renal artery clamp for 30min, and 3) drug treated Group (I/R+D) in which UK-350,926 (50 μg/kg.min) was infused I.V. for 30 min before and 2h after renal clamping. Results: Histological examinations of the kidneys showed mild degree of tissue damage in cortex of I/R group. There was marked apoptosis and disappearance of brush border in proximal tubular cells in this group that was not observed in I/R+D and sham group. Conclusion: These findings show that administration of the ETA antagonist, UK-350,926, improved the renal tissue damages that were parallel to improved reabsorptive function of the kidney.