?-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

ABSTRACT: Melanocyte-stimulating hormones, ?-, ?- and ?-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that ?-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of ?-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable ?-MSH analogue [Nle(4), D-Phe(7)]-?-MSH (NDP-?-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-?-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-?-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-?-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-?-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-?-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-?-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of ?-MSH analogues in the treatment of hypertension.

SUBMITTER: Rinne P 

PROVIDER: S-EPMC3745458 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature