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

Abstract

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 8–37, 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 8–37or 1-(5-isoquinolinylsulfonyl) -2-methylpiperazine. an inhibitor of protein kinase C. The present study suggests that the cardioproteclive 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.