Blocking cardiac ATP-sensitive K+ channels reduces hydroxyl radicals caused by potassium chloride-induced depolarization in the rat myocardium

The current study examined whether opening of the ATP-sensitive K+ (KATP) channel can induce hydroxyl free radical (OH) generation, as detected by increases in nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) levels in the rat myocardium. When KCl (4-140 mM) was administered to rat myocardium through microdialysis probe, the level of 2,3-DHBA increased gradually in a potassium ion concentration ([K+]o)-dependent manner. The [K+]o for half-maximal effect of the level of 2,3-DHBA production (ED50) was 67.9 μM. The maximum attainable concentration of the level of 2,3-DHBA (Emax) was 0.171 μM. Induction of glibenclamide (10 μM) decreased OH formation. The half-maximal inhibitory effect (IC50) for glibenclamide against the [K+]o (70 mM)-evoked increase in 2,3-DHBA was 9.2 μM. 5-Hydroxydecanoate (5-HD, 100 μM), another KATP channel antagonist, also decreased [K+]o-induced OH formation. The IC50 for 5-HD against the [K+]o (70 mM)-evoked increase in 2,3-DHBA was 107.2 μM. The heart was subjected to myocardial ischemia for 15 min by occlusion of left anterior descending coronary artery (LAD). When the heart was reperfused, the normal elevation of 2,3-DHBA in the heart dialysate was not observed in animals pretreated with glibenclamide (10 μM) or 5-HD (100 μM). These results suggest that opening of cardiac KATP channels by depolarization evokes OH generation.