Exploring the putative role of TRPV1 -dependent CGRP release in remote hind preconditioning-induced cardioprotection

Abstract

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 TRPV₁ -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_max , -dp/dt_min , and coronary flow rate. The pharmacological agents used in this study included capsaicin as TRPV₁ channel activator, sumatriptan and CGRP8-37 as CGRP blockers.

Results: Remote hind limb and capsaicin preconditioning (10 mg/kg^-1 ) significantly reduced the infarct size, LDH release, CK release and significantly improved LVDP, +dp/dt_max , -dp/dt_min , 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^-1 ) and CGRP8-37 (1 mg/kg^-1 ).

Conclusion: This indicates that remote hind limb preconditioning stimulus probably activates TRPV₁ channels which subsequently induces CGRP release to produce cardioprotective effects.

Keywords: CGRP; Capsaicin; Cardioprotection; Ischemia; Remote preconditioning; TRPV1 channels.