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 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 (1mg kg-1day-1)+1% NaCl for 3weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5mg kg-1day-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.
Keywords:
Aldosterone; Cardiac hypertrophy; ENaC; Mineralocorticoid receptor; Nedd4-2; Proanthocyanidins; SGK1.
Copyright © 2016 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Antihypertensive Agents / therapeutic use
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Antioxidants / therapeutic use
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Biomarkers / metabolism
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Cardiomegaly / etiology
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Cardiomegaly / prevention & control
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Cardiotonic Agents / therapeutic use
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Dietary Supplements*
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Endosomal Sorting Complexes Required for Transport / agonists
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Endosomal Sorting Complexes Required for Transport / antagonists & inhibitors*
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Endosomal Sorting Complexes Required for Transport / metabolism
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Epithelial Sodium Channel Agonists / antagonists & inhibitors
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Epithelial Sodium Channel Agonists / metabolism
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Epithelial Sodium Channel Blockers / therapeutic use
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Epithelial Sodium Channels / chemistry
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Epithelial Sodium Channels / metabolism*
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Fibrosis
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Heart Ventricles / immunology
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Heart Ventricles / metabolism*
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Heart Ventricles / pathology
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Heart Ventricles / physiopathology
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Hypertension / etiology
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Hypertension / prevention & control
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Immediate-Early Proteins / agonists
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Immediate-Early Proteins / antagonists & inhibitors*
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Immediate-Early Proteins / metabolism
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Male
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Mineralocorticoid Receptor Antagonists / therapeutic use
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Nedd4 Ubiquitin Protein Ligases
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Oxidative Stress
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Proanthocyanidins / therapeutic use*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Rats, Wistar
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Ubiquitin-Protein Ligases / antagonists & inhibitors*
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Ubiquitin-Protein Ligases / metabolism
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Ventricular Dysfunction, Left / metabolism
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Ventricular Dysfunction, Left / pathology
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Ventricular Dysfunction, Left / physiopathology
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Ventricular Dysfunction, Left / prevention & control*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antihypertensive Agents
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Antioxidants
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Biomarkers
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Cardiotonic Agents
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Endosomal Sorting Complexes Required for Transport
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Epithelial Sodium Channel Agonists
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Epithelial Sodium Channel Blockers
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Epithelial Sodium Channels
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Immediate-Early Proteins
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Mineralocorticoid Receptor Antagonists
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Proanthocyanidins
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NEDD4L protein, rat
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Nedd4 Ubiquitin Protein Ligases
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Nedd4 protein, rat
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Ubiquitin-Protein Ligases
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase