The protective effects of ischemic and calcitonin gene-related peptide-induced preconditioning on myocardial injury by endothelin-1 in the isolated perfused rat heart

This study was to investigate the effects of ischemic preconditioning on endothelin-1-induced myocardial injury and the role of calcitonin gene-related peptide (CGRP) played in such effects. The rat hearts were perfused in a Langendorff mode. Heart rates (HR). coronary flow (CF). left ventricular pressure (LVP) and its first derivative (LV dp/dt(max)) were recorded and creatinine phosphate kinase (CPK) from coronary effluent was measured. There were no changes in HR. CF, LVP. or LV dp/dt(max) throughout the experiment in the control hearts. Endothelin-1 (100 pmol) significantly decreased HR and CF. impaired the cardiac function, and increased the CPK release. However, the HR, CF, LVP and LV dp/dt(max) were significantly improved, while the CPK release was decreased in the preconditioned hearts. CGRP(x-37), a selective CGRP receptor antagonist, abolished the cardioprotection of ischemic preconditioning. such as the cardiac function and the CPK release. A similar cardioprotection was observed in the hearts pretreated with CGRP. However, the CGRP-induced preconditioning-like protection was abolished in the presence of CGRP(x-37) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C. The present study suggests that the cardioprotective effect of ischemic preconditioning on endothelin-1-induced myocardial injury is mediated by CGRP, and that the cardioprotection of CGRP-induced preconditioning is related to the activation of protein kinase C.