Hydrogen Sulfide Preconditioning Attenuates Ischemia/Reperfusion‐Induced Mitochondrial Dysfunction in Rat Intestine by a Bkca Channel‐Dependent Mechanism

The objectives of this study were to determine whether treatment with the hydrogen sulfide (H 2 S) donor NaHS (NaHS‐PC) 24 hrs prior to ischemia/reperfusion (I/R) would prevent postischemic mitochondrial dysfunction in rat intestinal mucosa and, if so, whether calcium‐activated, large conductance potassium (BK ca ) channels were involved in this protective effect. BK Ca expression in intestinal mucosa was detected by immunohistochemistry and western blotting. I/R was induced by 45‐min occlusion of the superior mesenteric artery (SMA) followed by 60‐min reperfusion in rats preconditioned with NaHS (0.8 mg/Kg, ip) 24 hrs earlier. Mitochondrial function was assessed by measuring the mitochondrial membrane potential (JC‐1), mitochondrial dehydrogenase function (MTT), and cytochrome c release. The protective effect of NaHS‐PC on postischemic mitochondrial function was abolished by coincident treatment with a BK ca channel inhibitor, paxilline (2.5 mg/Kg, ip). In addition, preconditioning with a BK ca channel activator (NS‐1619, 1 mg/Kg, ip) in lieu of NaHS‐PC was also effective in preventing I/R‐induced mitochondria dysfunction. Moreover, the protective effects of NS‐1619 preconditioning were abolished by coincident treatment with paxilline. Our data demonstrate that NaHS‐PC prevents postischemic mitochondrial dysfunction by a BK ca channel‐dependent mechanism.