title: Involvement of the central nervous system in the protective effect of melanocortins in myocardial ischaemia/reperfusion injury.
abstract: Melanocortin peptides exert, in rats, a protective effect in myocardial ischaemia followed by reperfusion, or permanent occlusion of a coronary artery. Moreover, melanocortins have an anti-shock effect. Since the mechanism of the life-saving effect of these peptides in haemorrhagic shock includes an essential brain loop, we aimed to determine whether the central nervous system (CNS) is also involved in the protective effect against the outcome of short-term myocardial ischaemia followed by reperfusion. Ischaemia was produced in anaesthetized rats by ligature of the left anterior descending coronary artery for 5 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF) and lethality, and the time-course of arterial blood pressure over 5 min following reperfusion were evaluated. Groups of 8-14 rats were used. Intravenous (i.v.) injection of ACTH-(1-24) (0.16-0.48 mg/kg) during the ischaemic period dose dependently reduced the incidence of VT, VF and of lethality. In saline-treated rats, coronary reperfusion caused VT in 100% animals, VF in 86%, and death in 86%. The highest dose of ACTH-(1-24) (0.48 mg/kg) completely prevented the occurrence of VT, VF and death in all rats (P<0.005). Moreover, the melanocortin peptide prevented the fall in mean arterial pressure (MAP) occurring during reperfusion. Treatment with ACTH-(1-24) by the intracerebroventricular (i.c.v.) route also reduced the incidence of VT, VF and lethality, and prevented the fall in MAP in a dose dependent manner. Complete (100%) protection occurred with an i.c.v. dose (0.048 mg/kg) 10 times less than that needed by the i.v. route. The present data show that in the protective effect of melanocortin peptides against the injury after myocardial ischaemia/reperfusion, the i.c.v. route of administration is more effective than the i.v. route. They suggest that a CNS mechanism, not yet identified, may be involved.
authors.affiliation: Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, via G. Campi 287, 41100 Modena, Italy. bazzani.carla@unimo.it
authors.forename: Carla
authors.initials: C
authors.lastname: Bazzani
authors.forename: Chiara
authors.initials: C
authors.lastname: Mioni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ferrazza
authors.forename: Maria Michela
authors.initials: MM
authors.lastname: Cainazzo
authors.forename: Alfio
authors.initials: A
authors.lastname: Bertolini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000494:pharmacology; D016019:Survival Analysis
chemical_list: D012965:Sodium Chloride; D000324:Adrenocorticotropic Hormone; D008012:Lidocaine