The Role of ATP-Sensitive Potassium Channels and Nitric Oxide in the Protective Effect of Preconditioning of the Brain

Abstract

Objective. The role of ATP-dependent potassium (K+ ATP) channels in the neuroprotective effect of ischemic (IPre) and pharmacological (PPre) preconditioning and changes in blood levels of nitric oxide (NO) metabolites were studied in conditions of cerebral ischemia. Materials and methods. Ischemic stroke (IS) was modeled in male rats (n = 86) by electrocoagulation of a branch of the middle cerebral artery (MCA). The nonselective K+ ATP channel blocker glibenclamide and the K+ ATP channel activator diazoxide were used. IPre and PPre were performed one day before MCA occlusion. Blood concentrations of NO, nitrates (NO3 –) and nitrites (NO2 –) were determined in experimental animals at 5, 24, and 72 h after MCA occlusion. Results. IPre decreased the lesion zone by 37% (p < 0.05), while prior administration of glibenclamide countered the action of IPre. The protective effect of PPre was analogous to that of IPre. Decreases in blood levels of oxygenated R-conformers of hemoglobin-bound NO (Hb-NO) were seen 5 h after MCA occlusion, with an inversely proportional increase in the concentration of nonoxygenated T-conformers; there were also increases in NO3 – and NO2 – concentrations. NO3 – and NO2 – levels showed normalization by one day after MCA occlusion, along with changes in the concentrations of Hb-NO complexes – R-conformers dominated, while the blood level of T-conformers reached a minimum. Furthermore, by 24 h there was a correlation between blockade of K+ ATP channels and decreases in serum NO3 – and NO2 – levels (p < 0.03). Conclusions. The neuroprotective effect of preconditioning was due to activation of K+ ATP channels. Analysis of blood levels of NO metabolites in rats with IS showed that Hb-NO complexes in the R-conformation stored and carried NO to the tissues, releasing NO on occurrence of the R → T transition in ischemic conditions.