Protective Effect of Melanocortin Peptides in Rat Myocardial Ischemia

• Published in: The Journal of pharmacology and experimental therapeutics 2001-06, Vol.297 (3), p.1082-1087
• Main Authors: Bazzani, Carla, Guarini, Salvatore, Botticelli, Annibale R., Zaffe, Davide, Tomasi, Aldo, Bini, Anna, Cainazzo, Maria Michela, Ferrazza, Giuseppe, Mioni, Chiara, Bertolini, Alfio
• Format: Article
• Language: English
• Subjects: alpha-MSH - administration & dosage; alpha-MSH - analogs & derivatives; Animals; Arrhythmias, Cardiac - prevention & control; Coronary Disease - drug therapy; Coronary Disease - metabolism; Cosyntropin - administration & dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography - drug effects; Electron Spin Resonance Spectroscopy; Female; Free Radicals - antagonists & inhibitors; Free Radicals - blood; Injections, Intravenous; Injections, Subcutaneous; Male; Myocardial Ischemia - drug therapy; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Reperfusion; Neuropeptides - administration & dosage; Rats; Rats, Wistar; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Survival Rate
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1016/S0022-3565(24)29636-1

The influence of the melanocortin peptide ACTH-(1-24) (adrenocorticotropin) on the consequences of short-term coronary ischemia (5 min) followed by reperfusion, and the effect of the long-acting melanocortin [Nle4,d-Phe7]α-melanocyte-stimulating hormone (NDP-MSH) on the damage induced by a permanent coronary occlusion, were investigated in anesthetized rats. Ischemia was produced by ligature of the left anterior descending coronary artery. Reperfusion-induced arrhythmias [ventricular tachycardia (VT), ventricular fibrillation (VF)] and survival rate within the 5 min following reperfusion, blood levels of free radicals detected 2 min after reperfusion by electron spin resonance spectrometry, and amount of healthy myocardial tissue, measured 72 h after permanent coronary occlusion on immunohistologically stained serial sections, were evaluated. Postischemic reperfusion induced VT in all saline-treated rats, and VF and death in a high percentage of animals (87%). In rats treated i.v. (2.5 min after coronary occlusion) with ACTH-(1-24) (0.16–0.48 mg/kg) there was a significantly dose-dependent reduction in the incidence of arrhythmias and lethality. Ischemia/reperfusion caused a large increase in free radical blood levels; treatment with ACTH-(1-24) (0.48 mg/kg i.v.) almost completely prevented this increase. In rats subjected to permanent coronary occlusion, the amount of healthy myocardial tissue was much reduced in saline-treated rats, while in rats treated s.c. with NDP-MSH (0.27 mg/kg every 12 h) it was significantly higher. The present data demonstrate, for the first time, an unforeseen property of melanocortin peptides, i.e., their ability to significantly reduce both heart ischemia/reperfusion injury and size of the ischemic area induced by permanent coronary occlusion.