MC3 receptors are involved in the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias

被引:38
作者
Guarini, S
Schiöth, HB
Mioni, C
Cainazzo, MM
Ferrazza, G
Giuliani, D
Wikberg, JES
Bertolini, A
Bazzani, C
机构
[1] Univ Modena & Reggio Emilia, Dept Biomed Sci, Pharmacol Sect, I-41100 Modena, Italy
[2] Univ Uppsala, Dept Neurosci, Uppsala, Sweden
[3] Uppsala Univ, Dept Pharmaceut Pharmacol, Uppsala, Sweden
关键词
melanocortin peptides; myocardium; ischemia/reperfusion; arrhythmias; MC3; receptors; rat;
D O I
10.1007/s00210-002-0572-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Myocardial ischemia/reperfusion induces ventricular tachycardia (VT), ventricular fibrillation (VF) and a high degree of lethality. Since ACTH-(1-24) (adrenocorticotropin) protects against such injuries in rats, we investigated which melanocortin MC receptor is involved. Ischemia was produced in anesthetized rats by ligature of the left anterior descending coronary artery (5 min), and reperfusion-induced VT, VF, lethality and time-course of arterial blood pressure within the 5 min following reperfusion were evaluated. I.v. administration of the selective MC3 receptor agonist gamma(1)-melanocyte-stimulating hormone (gamma(1)-MSH), as well as of an equimolar dose (162 nmol/kg) of both the non-selective agonist ACTH-(1-24) and alpha-MSH, significantly prevented VT and VF, and increased survival. Coronary reperfusion was followed by an abrupt and massive fall in mean arterial pressure and pulse pressure, in saline-treated rats. Treatment either with ACTH(1-24) or gamma(1)-MSH completely prevented such fall. The protective effect of ACTH-(1-24) against the occurrence of VT, VF and lethality was neither affected by adrenalectomy, nor by i.v. pretreatment with the selective MC4 receptor antagonist HS014 and the MC4-MC5 antagonist HS059. On the other hand, the MC3-MC4 receptor antagonist SHU 9119 prevented such protective effect. Moreover, the selective MC1 receptor agonist MS05 (162 nmol/kg i.v.) failed to reduce the incidence of arrhythmias and lethality. These data demonstrate that MC3 receptors mediate the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias, in rats.
引用
收藏
页码:177 / 182
页数:6
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