Calcitonin gene-related peptide-mediated cardioprotection of postconditioning in isolated rat hearts.
Previous studies have demonstrated that endogenous calcitonin gene-related peptide (CGRP) plays an important role in mediation of ischemic preconditioning. In the present study, we tested whether CGRP is also involved in mediation of the protective effects of postconditioning in isolated rat hearts. Sixty minutes of left coronary artery occlusion and followed by 60 min of reperfusion caused a significant decrease in cardiac function and a significant increase in creatine kinase (CK) release and infarct size. Postconditioning with three cycles of 1-min ischemia and 1-min reperfusion produced a marked improvement of cardiac function and decreased CK release and infarct size, concomitantly with an increase in the release of CGRP release in coronary effluent. However, the cardioprotection afforded by postconditioning was abolished by CGRP 8-37 (10(-7) M), a selective CGRP receptor antagonist, or pretreatment with capsaicin (50 mg/kg, s.c.), which depletes transmitters in sensory nerves. Exogenous CGRP (5 x 10(-9) M) administration of CGRP reappeared postconditioning-like cardioprotection in the rats pretreated with capsaicin. These results suggest that the protective effects of ischemic postconditioning are related to stimulation of endogenous CGRP release in rat hearts.
Li
Dai
D
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 110 Xiang-Ya Road, Changsha 410078, China.
Li
Nian-Sheng
NS
Chen
Qing-Quan
QQ
Guo
Ren
R
Xu
Ping-Sheng
PS
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left
D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide