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

Abstract

Introduction:The main goal of the study was to investigate the effect of KATP 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 (KATP) 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 KATP 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.