Proanthocyanidins Block Aldosterone-Dependent Upregulation of Cardiac Gamma Enac and Nedd4–2 Inactivation Via Sgk1

Abstract

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 type 1 (SGK1), epithelial Na + channel (γ-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/day) + 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/day). 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 SGK-1, 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.