Protection of calcitonin gene-related peptide-mediated preconditioning against coronary endothelial dysfunction induced by reperfusion in the isolated rat heart

This study was designed to explore the protective effect of ischemic precon ditioning on reperfusion-induced coronary endothelial dysfunction, with a f ocus on the role of calcitonin gene-related peptide (CGRP) in this effect, in the isolated perfused rat heart. Thirty minutes of global ischemia and 3 0 min of reperfusion significantly decreased heart rate, left ventricular p ressure, and its first derivative and impaired vasodilator responses to ace tylcholine. Ischemia-reperfusion did not affect vasodilator responses to so dium nitroprusside. Preconditioning induced by three cycles of 5 min of isc hemia and 5 min of reperfusion produced a significant improvement in cardia c function concomitantly with an amelioration of vasodilator responses to a cetylcholine. The protective effects of ischemic preconditioning were aboli shed by CGRP(8-37) (10(-7) M), the selective CGRP receptor antagonist. Afte r pretreatment with capsaicin (50 mg . kg(-1), s.c.) to deplete endogenous CGRP, the preconditioning effect was absent. Pretreatment with exogenous CG RP (5 X 10(-9) M) for 5 min induced a preconditioning-like protection. The present study suggests that the cardioprotection of ischemic preconditionin g is related to the preservation of the coronary endothelial cell, and that the protective effect of preconditioning is mediated by endogenous CGRP in the isolated perfused rat heart.