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: firstname.lastname@example.org).