Landiolol has cardioprotective effects against reperfusion injury in the rat heart via the PKC epsilon signaling pathway

摘要

Landiolol, a highly cardioselective beta 1-blocker, has cardioprotective effects against ischemia-reperfusion injury, although the precise mechanism is still unclear. The aim of this study was to clarify the cardioprotective mechanism of landiolol. Experiments were performed on Langendorff-perfused rat hearts undergoing 20 min stabilization, and 45 min of ischemia followed by 60 min of reperfusion. Various drugs with or without landiolol ( 100 mu M) were administered before ischemia for 20 min. Preischemic administration of landiolol reduced cardiac cellular damage and improved the recovery of cardiac function by about 40%. The alpha 1 blocker prazosin, the protein kinase C ( PKC) inhibitor chelerythrine or the K-ATP channel blocker glibenclamide, but not the selective mitochondrial KATP channel blocker 5-hydroxydecanoate abrogated the cardioprotective effect induced by landiolol. Following landiolol pretreatment the activation of PKC 1 and heat shock protein 27 were significantly higher than that in control. These data indicate that preischemic application of landiolol induces cardioprotective effects through PKC epsilon-mediated pathway, similar to that afforded by ischemic preconditioning.