Protection from renal ischemia reperfusion injury by an endothelin-A receptor antagonist BQ-123 in relation to nitric oxide production

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 l-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.