• Puneet Kaur Randhawa and Amteshwar Singh Jaggi.
• Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, India.
• Cardiovasc Ther. 2017 Oct 1; 35 (5).

BackgroundRemote 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.ObjectiveThis study aimed to inspect the putative involvement of TRPV1 -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection.MethodsIn 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/dtmax , -dp/dtmin , and coronary flow rate. The pharmacological agents used in this study included capsaicin as TRPV1 channel activator, sumatriptan and CGRP8-37 as CGRP blockers.ResultsRemote hind limb and capsaicin preconditioning (10 mg/kg-1 ) significantly reduced the infarct size, LDH release, CK release and significantly improved LVDP, +dp/dtmax , -dp/dtmin , 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 ).ConclusionThis indicates that remote hind limb preconditioning stimulus probably activates TRPV1 channels which subsequently induces CGRP release to produce cardioprotective effects.© 2017 John Wiley & Sons Ltd.

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