A1 Journal article – refereed
alpha-MSH Analogue Attenuates Blood Pressure Elevation in DOCA-Salt Hypertensive Mice




List of Authors: Rinne P, Penttinen AM, Nordlund W, Ahotupa M, Savontaus E
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2013
Journal: PLoS ONE
Journal name in source: PLOS ONE
Journal acronym: PLOS ONE
Number in series: 8
Volume number: 8
Issue number: 8
ISSN: 1932-6203

Abstract
Melanocyte-stimulating hormones, alpha-, beta- and gamma-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that alpha-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of alpha-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable alpha-MSH analogue [Nle(4), D-Phe(7)]-alpha-MSH (NDP-alpha-MSH) and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-alpha-MSH (0.3 mg/kg/day for 14 days) starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-alpha-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-alpha-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-alpha-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-alpha-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-alpha-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of alpha-MSH analogues in the treatment of hypertension.


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