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

• Published in: Life sciences (1973) 1999, Vol.64 (13), p.1091-1097
• Main Authors: Zhou, Fu-Wen, Li, Yuan-Jian, Lu, Rong, Deng, Han-Wu
• Format: Article
• Language: English
• Subjects: acetylcholine; Animals; calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - physiology; capsaicin; Coronary Vessels - physiopathology; endothelial injury; Endothelium, Vascular - physiology; Ischemic Preconditioning; ischemie preconditioning; Male; Myocardial Reperfusion Injury - prevention & control; Rats; Rats, Sprague-Dawley; Vasodilation
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(99)00037-5

This study was designed to explore the protective effect of ischemie preconditioning on reperfusion-induced coronary endothelial dysfunction, with a focus on the role of calcitonin gene-related peptide (CGRP) in this effect, in the isolated perfused rat heart. Thirty minutes of global ischemia and 30 min of reperfusion significantly decreased heart rate, left ventricular pressure, and its first derivative and impaired vasodilator responses to acetylcholine. Ischemia reperfusion did not affect vasodilator responses to sodium nitroprusside. Preconditioning induced by three cycles of 5 min of ischemia and 5 min of reperfusion produced a significant improvement in cardiac function concomitantly with an amelioration of vasodilator responses to acetylcholine. The protective effects of ischemie preconditioning were abolished by CGRP 8–37 (10 −7 M), the selective CGRP receptor antagonist. After pretreatment with capsaicin (50 mg · kg −1, s.c.) to deplete endogenous CGRP, the preconditioning effect was absent. Pretreatment with exogenous CGRP (5 × 10 −9 M) for 5 min induced a preconditioning-like protection. The present study suggests that the cardioprotection of ischemie preconditioning 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.