Protective effect of melanocortin peptides in rat myocardial ischemia.
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 [Nle(4),D-Phe(7)]alpha-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.
Bazzani
C
C
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
Guarini
S
S
Botticelli
A R
AR
Zaffe
D
D
Tomasi
A
A
Bini
A
A
Cainazzo
M M
MM
Ferrazza
G
G
Mioni
C
C
Bertolini
A
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D003366:Cosyntropin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000097:blood; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015425:Myocardial Reperfusion; D009479:Neuropeptides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D015996:Survival Rate; D000521:alpha-MSH / Q000008:administration & dosage* / Q000031:analogs & derivatives
D005609:Free Radicals; D009479:Neuropeptides; D003366:Cosyntropin; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-