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MC(3) receptors are involved in the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2002 Aug; Vol. 366 (2), pp. 177-82. Date of Electronic Publication: 2002 May 24. - Publication Year :
- 2002
-
Abstract
- 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 MC(3) 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 MC(4) receptor antagonist HS014 and the MC(4)-MC(5) antagonist HS059. On the other hand, the MC(3)-MC(4) receptor antagonist SHU 9119 prevented such protective effect. Moreover, the selective MC(1) receptor agonist MS05 (162 nmol/kg i.v.) failed to reduce the incidence of arrhythmias and lethality. These data demonstrate that MC(3) receptors mediate the protective effect of melanocortins in myocardial ischemia/reperfusion-induced arrhythmias, in rats.
- Subjects :
- Animals
Arrhythmias, Cardiac metabolism
Arrhythmias, Cardiac mortality
Blood Pressure drug effects
Blood Pressure physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Heart Rate drug effects
Heart Rate physiology
Injections, Intravenous
Male
Myocardial Ischemia metabolism
Myocardial Ischemia mortality
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury mortality
Rats
Rats, Wistar
Receptor, Melanocortin, Type 3
Receptors, Corticotropin agonists
Receptors, Corticotropin antagonists & inhibitors
Receptors, Corticotropin metabolism
Adrenocorticotropic Hormone pharmacology
Arrhythmias, Cardiac prevention & control
Myocardial Ischemia drug therapy
Myocardial Reperfusion Injury prevention & control
Receptors, Corticotropin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 366
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12122505
- Full Text :
- https://doi.org/10.1007/s00210-002-0572-8