Late anti-apoptotic effect of K(ATP) channel opening in skeletal muscle.

Necrosis and apoptosis caused by ischaemia-reperfusion (IR) result in myocyte death and atrophy. ATP-sensitive K(+) (K(ATP) ) channels activation increases tissue tolerance of IR-injury. Thus, in the present study, we evaluated the effects of K(ATP) channel activation on skeletal muscle apoptosis after IR. Male Wistar rats were treated with 40 mg/kg, i.p., diazoxide (a K(ATP) channel opener) or 5 mg/kg, i.p., glibenclamide (a K(ATP) channel inhibitor) 30 min before the induction of 3 h ischaemia, followed by 6, 24 or 48 h reperfusion. At the end of the reperfusion period, the gastrocnemius muscle was removed for the analysis of tissue malondialdehyde content, superoxide dismutase (SOD) and catalase (CAT) activity, Bax and Bcl-2 protein expression, histological damage and the number of apoptotic nuclei. Ischaemia-reperfusion increased malondialdehyde content (P < 0.01) and Bax expression (P < 0.01) and induced severe histological damage, in addition to decreasing CAT and SOD activity (P < 0.01 and P < 0.05, respectively) and Bcl-2 expression (P < 0.01). Diazoxide reversed the effects of IR on tissue damage, MDA content, SOD and CAT activity (after 6 and 24 h reperfusion; P < 0.05) and Bax and Bcl-2 expression (after 24 and 48 h reperfusion; P < 0.01). In contrast, glibenclamide pretreatment had no effect. The number of apoptotic nuclei in the IR and glibenclamide-pretreated groups increased significantly (P < 0.001 vs Sham). In contrast, diazoxide pretreatment decreased the number of apoptotic nuclei compared with the IR group (P < 0.01). The results of the present study suggest that the K(ATP) channel activator diazoxide attenuates lipid peroxidation during the first hour of reperfusion and modulates apoptotic pathways at later time points.