The aim of this study was to investigate whether the protective effect of endothelin-A (ETA) receptor antagonist BQ-123 against renal ischemia reperfusion (I/R) injury is related to nitric oxide (NO) production. Sprague-Dawley rats were divided into six,groups: control, I/R, N sup omega nitro-L-arginine methyl ester (L-NAME), BQ, BQ + L-NAME, BQ + L-NAME + L-Arg groups. After urethane anesthesia, 30 min renal ischemia and 2 h reperfusion were performed in all groups except control group. Mean arterial pressures (MAP) during reperfusion in all L-NAME-treated groups were higher than during pre-ischemia and ischemia, however, MAP at 60th and 120th minute of reperfusion in control and BQ groups were lower than during ischemia. MAP Of NAME-treated groups were significantly higher than the other groups during reperfusion period. The I/R caused lipid peroxidation and protein oxidation, however, BQ-123 treatment prevented oxidant injury. The inhibition of NO production prevented effect of BQ- 123 treatment. Also, BQ-123 treatment caused an increase in superoxide dismutase and catalase activities. Both BQ- 123 and L-NAME treatments prevented high xanthine oxidase activity. BQ-123 prevented risen myeloperoxidase activity and L-NAME reversed this effect of BQ-123 just like the addition Of L-arginine to the treatment altered the effect Of L-NAME. The plasma BUN was affected as increasing manner from L-NAME treatments; on the other hand, plasma Cr and Na. concentrations were affected as decreasing manner from BQ-123 treatments. ETA receptor antagonist BQ-123 may be revealed a protective agent against renal I/R injury with a possible secondary pathway via its antioxidant effects. We suggest that BQ-123 may mediate the protective effect via a NO-dependent mechanism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.