Investigating the involvement of glycogen synthase kinase-3β and gap junction signaling in TRPV1 and remote hind preconditioning-induced cardioprotection.

Remote ischemic preconditioning (RIPC) is the phenomenon that harnesses the body's endogenous protective mechanisms against prolonged ischemia-reperfusion-induced injury. The present study aimed to explore the involvement of glycogen synthase kinase-3β and gap junction signaling in TRPV1 and remote hind preconditioning-induced cardioprotection. In the present study, four consecutive cycles (5min of ischemia-reperfusion) of remote hind limb preconditioning stimulus were delivered using a blood pressure cuff fastened at the inguinal level of the rat. The isolated rat hearts were mounted on the Langendorff's apparatus and were exposed to 30min of global ischemia-120min of reperfusion. Sustained ischemia-reperfusion led to cardiac injury that was assessed in terms of infarct size, LDH release, CK release, LVDP, +dp/dtmax, -dp/dtmin, heart rate and coronary flow rate. The pharmacological agents employed in the present study included capsaicin (10mg/kg) as TRPV1 channel activator, AR-A014418 (1 and 3mg/kg) as glycogen synthase kinase-3β inhibitor and carbenoxolone disodium (50 and 100mg/kg) as gap junction blocker. Remote hind limb, capsaicin and AR-A014418 preconditioning led to significant reduction in the infarct size, LDH release, CK release and improved LVDP, +dp/dtmax, -dp/dtmin, heart rate and coronary flow rate. However, remote hind limb, capsaicin and AR-A014418 preconditioning-induced cardioprotective effects were remarkably reduced in the presence of carbenoxolone (100mg/kg). This indicates that remote preconditioning stimulus probably activates TRPV1 channels that may inhibit glycogen synthase kinase-3β activity which subsequently enhances gap junction coupling to produce cardioprotective effects.