Opening of mitochondrial [K.sub.ATP] channel induces early and delayed cardioprotective effect: role of nitric oxide

Ockaili, Ramzi, Venkata R. Emani, Shinji Okubo, Michael Brown, Kavitha Krottapalli, and Rakesh C. Kukreja. Opening of mitochondrial [K.sub.ATP] channel induces early and delayed cardioprotective effect: role of nitric oxide. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H2425-H2434, 1999.--Opening of mitochondrial ATP-sensitive (mito[K.sub.ATP]) channel with diazoxide induces an early phase (EP) of cardioprotection. It is unknown whether diazoxide also induces a delayed phase (DP) of cardioprotection. Because nitric oxide (NO) modulates ATP sensitivity of the [K.sub.ATP] channel, we hypothesized that NO may play a role in diazoxide-induced cardioprotection. Diazoxide (1 mg/kg) was administered either 30 min (for EP) or 24 h (DP) before 30 min of lethal ischemia. Blockers of mito[K.sub.ATP] channel [5-hydroxydecanoate (5-HD)] or NO synthase [[N.sup.G]-nitro-L-arginine methyl ester (L-NAME)] were given 10 min before ischemia-reperfusion performed by 30 min of left anterior descending coronary artery occlusion and 3 h of reperfusion. A risk area (RA) was demarcated by Evans blue dye, and infarct size (IS) was measured by tetrazolium staining. Diazoxide caused a decrease in IS (%RA) from 27.8 [+ or -] 4.2% in the vehicle group to 12.9 [+ or -] 1.2% during EP and from 30.4 [+ or -] 4.2% in vehicle-treated rabbits to 19.6 [+ or -] 2.4% during DP (P [is less than] 0.05). IS increased to 31.3 [+ or -] 1.1% and 27.9 [+ or -] 1.0% (EP) and 29.9 [+ or -] 2.3% and 35.1 [+ or -] 1.8% (DP) with 5-HD and L-NAME, respectively (P [is less than] 0.05). 5-HD and L-NAME caused no proischemic effect in controls. Diazoxide induced both early and delayed anti-ischemic effects via opening of mito[K.sub.ATP] channels, which was NO dependent. mitochondria; adenosine 5'-triphosphate-sensitive potassium channel; ischemia-reperfusion; infarction