Role of mitochondrial permeability transition pore and mitochondrial ATP-sensitive potassium channels in the protective effects of ischemic preconditioning in isolated hearts from fed and fasted rats

The aim of the present study was to assess whether the protective effects of ischemic preconditioning (PC) are associated with activation of the mitochondrial ATP-sensitive potassium channels (mitoKATP) and if there is any relationship between the activity of these channels and the mitochondrial permeability transition pore (MPTP) opening in ischemic-reperfused rat hearts under different nutritional conditions. Langendorff-perfused hearts of fed and 24-h fasted rats were exposed to 25 min of no-flow global ischemia plus 30 min of reperfusion. Fasting accelerated functional recovery and attenuated MPTP opening. The mitoKATP blocker, 5-hydroxydecanoic (HD), did not influence functional recovery and MPTP opening induced by ischemia-reperfusion in the fed hearts but partially reversed the beneficial effects of fasting. PC and the mitoKATP opener, diazoxide (DZ), improved functional recovery, preserved cell viability, and inhibited MPTP opening in both fed and fasted hearts. The protection elicited by PC and DZ on contractile recovery and MPTP opening was reversed by HD, which did not affect cell viability. Altogether, these results argue for a role of mitoKATP and its impact on preservation mitochondrial inner membrane permeability as a relevant factor in the improvement of contractile function in the ischemic-reperfused rat heart. They also suggest that the functional protection elicited by PC may be related to this mechanism

Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic-reperfused heart of fed and fasted rats

This investigation aimed to assess whether the mitochondrial ATP-sensitivepotassium channel blocker 5-hydroxydecanoate (5-HD) could abolish the protectionconferred by fasting and ischemic preconditioning (IPC) and to ascertainwhether these effects are associated with glycogen breakdown and glycolytic activity.Langendorff perfused hearts of fed and 24-h fasted rats were exposed to 25 minischemia plus 30 min reperfusion. IPC was achieved by a 3 min ischemia plus a 5 minreperfusion cycle. 5-HD (100 µM) perfusion begun 5 min before IPC or 13 minbefore sustained ischemia in the non preconditioned groups. Fasting improved thereperfusion recovery of contraction, decreased the contracture and the lactate production,increased glycogenolysis and did not affect the percentage of viable tissue.5-HD abolished the effects of fasting on the contractile recovery but did not affectthe contracture. 5-HD decreased the lactate production in the fed group, increasedthe preischemic glycogen content in both nutritional groups and did not affect theischemic glycogen fall. IPC improved the contractile function but prevented thecontracture only in the fed group, reduced lactate accumulation and glycogenolysisand evoked an increase of the viable tissue. 5-HD abolished the effects of IPC on thecontractile recovery and did not affect its effect on the contracture, lactate production,glycogenolysis and viable tissue. These data suggest that the mitocondrial ATPsensitivepotassium channel is involved in the effects of fasting and IPC on the contractilefunction but the other cardioprotective and metabolic effects appear evokedthrough other mechanisms. Also suggest that besides the inhibition of the mitochondrialpotassium channel, other mechanisms mediate the effects of 5-HD (AU)

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