Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: Intravital microscopic observation and 31P-MR spectroscopic studies

Aims: Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We investigated the ameliorating effect of CGRP in myocardial ischemia induced by endothelin-1 (ET-1), with special emphasis on myocardial microvascular hemodynamics and levels of energy-related metabolites. Main methods: The Langendorff preparations of rat isolated heart were perfused at a constant flow rate. Microvascular blood flow was also visualized in the anterior epicardium of the left ventricle by means of an intravital fluorescence microscope system. Energy-related metabolite contents in the myocardium were measured by means of P-31-magnetic resonance spectroscopy (P-31-MRS). Key findings: Intracoronary bolus injections of CGRP caused dose-dependent decreases in coronary perfusion pressure (CPP) in the hearts exposed to ET-1 (30 pmol). The vasodilator potency of CGRP was about 10,000-fold greater than that of nitroglycerin and 1,000-fold greater than that of isobutylmethylxanthine. Vasodilation of the small-sized arterioles (10-40 mu m in diameter) in response to CGRP (100 pmol) was confirmed by direct microscopic observation. After ET-1 (30 pmol) plus vehicle administration, high energy phosphates (phosphocreatine (PCr). ATP) were markedly reduced (p < 0.05). CGRP administration significantly (p< 0.05) attenuated the anaerobic changes in the myocardium (decrease in PCr) and macrohemodynamic alterations (increase in CPP, decrease in dP/dt etc.) induced by ET-1. Significance: We conclude that CGRP effectively confers hemodynamic and metabolic protections to isolated beating hearts against ET-1-induced myocardial ischemia. (C) 2014 The Authors. Published by Elsevier Inc.