title: Proanthocyanidins block aldosterone-dependent up-regulation 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 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.
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Adrián
authors: A
authors: Galiana-Simal
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Elena
authors: E
authors: Olivares-Álvaro
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Mercedes
authors: M
authors: Klett-Mingo
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: María Belén
authors: MB
authors: Ruiz-Roso
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Sandra
authors: S
authors: Ballesteros
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Natalia
authors: N
authors: de Las Heras
authors: Hudson Institute of Medical Research, Clayton, VIC 3168, Australia.
authors: Peter J
authors: PJ
authors: Fuller
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors: Vicente
authors: V
authors: Lahera
authors: Department of Physiology, Faculty of Medicine, Universidad Complutense, 28040 Madrid, Spain. Electronic address: bmartinfernandez@med.ucm.es.
authors: Beatriz
authors: B
authors: Martín-Fernández
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000627:therapeutic use; D019587:Dietary Supplements; D056827:Endosomal Sorting Complexes Required for Transport / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062708:Epithelial Sodium Channel Agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D062686:Epithelial Sodium Channel Blockers / Q000627:therapeutic use; D053503:Epithelial Sodium Channels / Q000737:chemistry / Q000378:metabolism*; D005355:Fibrosis; D006352:Heart Ventricles / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D017874:Immediate-Early Proteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D000075702:Nedd4 Ubiquitin Protein Ligases; D018384:Oxidative Stress; D044945:Proanthocyanidins / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017208:Rats, Wistar; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D056827:Endosomal Sorting Complexes Required for Transport; D062708:Epithelial Sodium Channel Agonists; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D000451:Mineralocorticoid Receptor Antagonists; D000075702:Nedd4 Ubiquitin Protein Ligases; D044945:Proanthocyanidins; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D000099184:Serum-Glucocorticoid Regulated Kinases; C000618479:NEDD4L protein, rat; C000618484:Nedd4 protein, rat
keywords: Aldosterone; Cardiac hypertrophy; ENaC; Mineralocorticoid receptor; Nedd4-2; Proanthocyanidins; SGK1