Proanthocyanidins block aldosterone-dependent up-regulation of cardiac gamma ENaC and Nedd4-2 inactivation via SGK1

卷:37

Galiana-Simal, Adrian ; Olivares-Alvaro, Elena ; Klett-Mingo, Mercedes ; Belen Ruiz-Roso, Maria ; Ballesteros, Sandra ; de Las Heras, Natalia ; Fuller, Peter J. ; Lahera, Vicente ; Martin-Fernandez, Beatriz

Univ Complutense

关键词: Proanthocyanidins;    Aldosterone;    Mineralocorticoid receptor;    Cardiac hypertrophy;    SGK1;    ENaC;    Nedd4-2;   

DOI  :  10.1016/j.jnutbio.2016.07.012

学科分类：食品科学和技术

【 摘 要 】

Aldosterone plays a central role in the development of cardiac pathological states involving ion transport imbalances, especially sodium transport. We have previously demonstrated a cardioprotective effect of proanthocyanidins in aldosterone-treated rats. Our objective was to investigate for the first time the effect of proanthocyanidins on serum and glucocorticoid-regulated kinase 1 (SGK1), epithelial Na+ channel (gamma-ENaC), neuronal precursor cells expressed developmentally down-regulated 4-2 (Nedd4-2) and phosphoNedd4-2 protein expression in the hearts of aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg(-1) day(-1))+1% NaCl for 3 weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg-1 day-1). Hypertension and diastolic dysfunction induced by aldosterone were abolished by treatment with PRO80. Expression of fibrotic, inflammatory and oxidative mediators were increased by aldosterone-salt administration and blunted by PRO80. Antioxidant capacity was improved by PRO80. The up-regulated aldosterone mediator SGK1, ENaC and p-Nedd4-2/total Nedd4-2 ratio were blocked by PRO80. PRO80 blunted aldosterone-mineralocorticoid-mediated up-regulation of ENaC provides new mechanistic insight of the beneficial effect of proanthocyanidins preventing the cardiac alterations induced by aldosterone excess. (C) 2016 Elsevier Inc. All rights reserved.