Exploring the putative role of TRPV -dependent CGRP release in remote hind preconditioning-induced cardioprotection.

BACKGROUND

Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient nonlethal ischemia and reperfusion episodes confer protection against prolonged ischemia reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored.

OBJECTIVE

This study aimed to inspect the putative involvement of TRPV -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection.

METHODS

In this study, remote hind limb preconditioning stimulus was delivered (four consecutive episodes of 5 minutes of ischemia reperfusion) using a blood pressure cuff tied at the inguinal level of the rat. The isolated rat hearts were perfused on the Langendorff's system and were subjected to 30-minutes global ischemia and 120-minutes reperfusion. Prolonged ischemia and subsequent reperfusion led to myocardial injury that was evaluated in terms of infarct size, LDH release, CK release, LVDP, +dp/dt , -dp/dt , and coronary flow rate. The pharmacological agents used in this study included capsaicin as TRPV channel activator, sumatriptan and CGRP8-37 as CGRP blockers.

RESULTS

Remote hind limb and capsaicin preconditioning (10 mg/kg ) significantly reduced the infarct size, LDH release, CK release and significantly improved LVDP, +dp/dt , -dp/dt , and coronary flow rate. However, remote hind limb and capsaicin preconditioning-induced cardioprotective effects were remarkably reduced in the presence of sumatriptan (8 mg/kg ) and CGRP8-37 (1 mg/kg ).

CONCLUSION

This indicates that remote hind limb preconditioning stimulus probably activates TRPV channels which subsequently induces CGRP release to produce cardioprotective effects.