Gene differences in resistance to ischemia‐reperfusion injury in Brown Norway rats

Oxidative stress mediates ischemia-reperfusion (IR) injury, but it is not clear if imbalances in oxidant production and disposal account for resistance vs. susceptibility to IR injury. The purpose of this study was to evaluate expression of enzymes that produce superoxide (O2·−) (i.e. xanthine oxidase) or detoxify it (i.e. copper zinc superoxide dismutase, CuZn SOD; manganese superoxide dismutase, MnSOD) in IR-resistant BN rats vs. Sprague Dawley (SD) rats. As O2·− interacts with nitric oxide (NO) to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also examined. Renal arteries of SD and BN rats were clamped for 45 minutes with reperfusion for 24 hours. After IR, serum creatinine was elevated (P<0.01) only in the SD rats. Although there was an insignificant decrease in MnSOD, CuZn SOD was lower (P<0.05) after IR in the SD rats vs. BN or shams. Both iNOS and xanthine oxidase were elevated (P<0.01) after IR only in the SD group. Slot blot analysis revealed increased nitrotyrosine, after IR in SD vs. BN or sham controls. Collectively these results show that the resistance to renal IR in BN rats is associated with preserved antioxidant defenses and decreased oxidant production.