A1 Journal article – refereed
Hemodynamic actions and mechanisms of systemically administered alpha-MSH analogs in mice




List of Authors: Rinne P, Tikka S, Makela S, Streng T, Savontaus E
Publisher: ELSEVIER SCIENCE INC
Publication year: 2012
Journal: Peptides
Journal name in source: PEPTIDES
Journal acronym: PEPTIDES
Number in series: 1
Volume number: 38
Issue number: 1
Number of pages: 9
ISSN: 0196-9781

Abstract
alpha-Melanocyte-stimulating hormone (alpha-MSH) regulates important physiological functions including energy homeostasis and inflammation. Potent analogs of alpha-MSH, [NIe(4), D-Phe(7)]-alpha-MSH (NDP-alpha-MSH) and melanotan-II (MT-II), are widely used in pharmacological studies, but the hemodynamic effects associated with their systemic administration have not been thoroughly examined. Therefore, we investigated the hemodynamic actions of these compounds in anesthetized and conscious C57B1/6N mice using peripheral routes of administration. NDP-alpha-MSH and MT-II induced mild changes in blood pressure and heart rate in anesthetized mice compared to the effects observed in conscious mice, suggesting that anesthesia distorts the hemodynamic actions of alpha-MSH analogs. In conscious mice, NDP-alpha-MSH and MT-II increased blood pressure and heart rate in a dose-dependent manner, but the tachycardic effect was more prominent than the pressor effect. Pretreatment with the melanocortin (MC) 3/4 receptor antagonist SHU9119 abolished these hemodynamic effects. Furthermore, the blockade of beta(1)-adrenoceptors with metoprolol prevented the pressor effect and partly the tachycardic action of alpha-MSH analogs, while the ganglionic blocker hexamethonium abrogated completely the difference in heart rate between vehicle and alpha-MSH treatments. These findings suggest that the pressor effect is primarily caused by augmentation of cardiac sympathetic activity, but the tachycardic effect seems to involve withdrawal of vagal tone in addition to sympathetic activation. In conclusion, the present results indicate that systemic administration of alpha-MSH analogs elevates blood pressure and heart rate via activation of MC3/4 receptor pathways. These effects and the consequent increase in cardiac workload should be taken into account when using alpha-MSH analogs via peripheral routes of administration. (C) 2012 Elsevier Inc. All rights reserved.


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