Early and delayed cardioprotection by heat stress is mediated by calcitonin gene-related peptide.
Brief ischaemia or heat stress protects the myocardium against ischaemia-reperfusion injury. Heat stimulus evokes release of sensory nerve transmitters, including calcitonin gene-related peptide (CGRP). Since CGRP has been shown to play an important role in the mediation of ischaemic preconditioning, the present study examined whether early or delayed preconditioning induced by retrograde hyperthermic perfusion in vitro or by whole-body hyperthemia in vivo also involves endogenous CGRP. Isolated rat hearts were perfused in the Langendorff mode and subjected to 30 min global ischaemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure and its first derivatives (+/-dp/dt) were recorded and the CGRP-like immunoreactivity (CGRP-LI) content and the release of creatine kinase (CK) during reperfusion were measured. Retrograde hyperthermic perfusion (42 degrees C) for 5 min improved the recovery of cardiac function, decreased the release of CK and elevated the content of CGRP-LI in the coronary effluent. CGRP(8-37) (10(-7 mol/l), a selective CGRP receptor antagonist, abolished the cardioprotection by heat stress. Pretreatment with capsaicin (50 mg/kg s.c.), which specifically depletes sensory nerve transmitter content, abolished both the cardioprotection and the increased release of CGRP-LI. Whole-body hyperthermia (42 degrees C for 15 min) caused an increase in the plasma concentration of CGRP-LI. Early or delayed protection was shown in the hearts obtained from the animals subjected to whole-body hyperthermia 10 min or 48 h before the experiments. The early or delayed protection by heat stress was also abolished by pretreatment with capsaicin. The present study suggests that, in the rat, the early and delayed cardioprotection induced by heat stress involves endogenous CGRP.
Song
Q J
QJ
Department of Pharmacology, Hunan Medical University, Changsha, P.R. China.
Li
Y J
YJ
Deng
H W
HW
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D005334:Fever / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D018882:Heat Stress Disorders / Q000503:physiopathology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000502:physiology
D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide