Early and delayed cardioprotection by heat stress is mediated by calcitonin gene-related peptide

Brief ischaemia or heat stress protects the myocardium against ischaemia-re perfusion injury. Heat stimulus evokes release of sensory nerve transmitter s, including calcitonin gene-related peptide (CGRP). Since CGRP has been sh own to play an important role in the mediation of ischaemic preconditioning . the present study examined whether early or delayed preconditioning induc ed by retrograde hyperthermic perfusion in vitro or by whole-body hyperthem ia in vivo also involves endogenous CGRP. Isolated rat hearts were perfused in the Langendorff mode and subjected to 30 min global ischaemia and 30 mi n reperfusion. Heart rate, coronary flow, left ventricular pressure and its first derivatives (+/-dp/dt) were recorded and the CGRP-like immunoreactiv ity (CGRP-LI) content and the release of creatine kinase (CK) during reperf usion 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 cardiopr otection by heat stress. Pretreatment with capsaicin (50 mg/kg s.c.), which specifically depletes sensory nerve transmitter content, abolished both th e cardioprotection and the increased release of CGRP-LI. Whole-body hy pert hermia (42 degrees C for 15 min) caused an increase in the plasma concentra tion of CGRP-LI. Early or delayed protection was shown in the hearts obtain ed from the animals subjected to whole-body hyperthermia 10 min or 48 h bef ore the experiments. The early or delayed protection by heat stress was als o 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.