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/dtmax) were recorded and creatinine phosphate kinase (CPK) from coronary effluent was measured. There were no changes in HR, CF, LVP, or LV dp/dtmax 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/dtmax were significantly improved, while the CPK release was decreased in the preconditioned hearts. CGRP8-37, 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 CGRP8-17 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.
Department of Pharmacology, Hunan Medical University, Changsha, P.R. China.
C F
CF
Peng
Y J
YJ
Li
H W
HW
Deng
Y
Y
Xiong
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D019332:Endothelin-1 / Q000502:physiology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide