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Structural, Functional, and Molecular Alterations Produced by Aldosterone Plus Salt in Rat Heart: Association With Enhanced Serum and Glucocorticoid–regulated Kinase-1 Expression

Martín-Fernández, Beatriz PhD*; de las Heras, Natalia PhD, DSc*; Miana, María PhD, DSc*; Ballesteros, Sandra BSc*; Delgado, Carmen PhD, DSc†‡; Song, Su PhD§; Hintze, Thomas PhD, DSc§; Cachofeiro, Victoria PhD, DSc*; Lahera, Vicente BSc*

Journal of Cardiovascular Pharmacology: January 2011 - Volume 57 - Issue 1 - p 114-121
doi: 10.1097/FJC.0b013e31820088ca
Original Article

We aimed to evaluate the structural, functional, inflammatory, and oxidative alterations, as well as serum and glucocorticoid-regulated kinase-1 (SGK-1) expression, produced in rat heart by aldosterone + salt administration. Fibrosis mediators such as connective tissue growth factor, matrix metalloproteinase 2, and tissue inhibitor of metalloproteinases 2 were also evaluated. Treatment with spironolactone was evaluated to prove mineralocorticoid mediation. Male Wistar rats received aldosterone (1 mg·kg−1·d−1) + 1% NaCl for 3 weeks. Half of the animals were treated with spironolactone (200 mg·kg−1·d−1). Systolic and diastolic blood pressures, left ventricle (LV) systolic pressure, and LV end-diastolic pressure were elevated (P < 0.05) in aldosterone + salt-treated rats. In aldosterone + salt-treated rats, -dP/dt decreased (P < 0.05), but +dP/dt was similar in all groups. Spironolactone normalized (P < 0.05) systolic blood pressure, diastolic blood pressure, LV systolic pressure, LV end-diastolic pressure, and -dP/dt. Relative heart weight, collagen content, messenger RNA expression of transforming growth factor beta, connective tissue growth factor, matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 2, tumor necrosis factor alpha, interleukin-1β, p22phox, endothelial nitric oxide synhtase, and SGK-1 were increased (P < 0.05) in aldosterone + salt-treated rats, being reduced by spironolactone (P < 0.05). SGK-1 might be a key mediator in the structural, functional, and molecular cardiac alterations induced by aldosterone + salt in rats. All the observed changes and mediators are related with the activation of mineralocorticoid receptors.

From the *Departments of Physiology; and †Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain; ‡Centro de Investigaciones Biológicas (CSIC), Madrid, Spain; and §Department of Physiology, New York Medical College, Valhalla, NY.

Received for publication July 6, 2010; accepted October 6, 2010.

Supported by grants from Comisión Interministerial de Ciencia y Tecnología de España (SAF2007-61595), Fondo de Investigaciones Sanitarias (FIS PI 09/0871), and Red Cardiovascular del Fondo de Investigaciones Sanitarias (RD06/0014/0007).

Conflict of interest: None.

Reprints: Vicente Lahera, BSc, Departamento de Fisiología, BSc, Facultad de Medicina, Universidad Complutense, Madrid 28040 Spain (e-mail:

© 2011 Lippincott Williams & Wilkins, Inc.