Modulators of K-ATP channels in the prevention of oxidative stress and antioxidant capacity improvement in the rat heart with different resistance to hypoxia upon cobalt treatment

摘要

Introduction: The main goal of the study was to investigate the effect of K-ATP channel modulators on development of oxidative stress in the heart of rats showing different resistance to hypoxia. Material and Methods: The study has been performed on rats showing high- (HR) or low-resistance (LR) to hypoxia under modulators of ATP-sensitive potassium (K-ATP) channel opener pinacidil (0.06 mg/kg) and blocker glibenclamide (1 mg/kg) upon cobalt (Co) treatment (30 mg of cobalt chloride/kg b.w., 3 h). Changes in the oxidative stress parameters of the heart tissue, such as lipid peroxidation (LPO), level of oxidatively modified protein (OMP), and antioxidant defence system (superoxide dismutase - SOD, catalase -CAT, glutathione peroxidase - GPx, glutathione reductase - GR) as well as total antioxidant activity (TAA) were analysed. Results: Co treatment caused a significant decrease in SOD and CAT activity in the heart of LR rats and GPx activity in HR rats. It also led to a decrease in OMP level in the heart of rats with HR in comparison with controls. Conclusion: The obtained results suggest that individual resistance to hypoxia plays a crucial role in Co actions and provides evidence that the effects of K-ATP channel opener pinacidil in the heart are mediated through different pathways of the antioxidative system, depending on the individual resistance to hypoxia. Pinacidil exerts a protective effect on the heart tissue by preventing the LPO decrease and significantly reducing OMP levels, as well as increasing TTA in rats with LR.