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Type: Artigo
Title: Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum‐ and glucocorticoid‐regulated kinase type 1
Author: Martin-Fernandez, Beatriz
de las Heras, Natalia
Miana, Maria
Ballesteros, Sandra
Valero-Munoz, Maria
Vassallo, Dalton
Davel, Ana Paula
Rossoni, Luciana Venturini
Cachofeiro, Victoria
Lahera, Vicente
Abstract: Persistent beta-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg-1 day-1) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg-1 day-1). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor beta, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor a, interleukin 1 beta, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats
Subject: Isoproterenol
Country: Reino Unido
Editor: Wiley
Rights: Fechado
Identifier DOI: 10.1113/expphysiol.2011.063230
Date Issue: 2012
Appears in Collections:IB - Artigos e Outros Documentos

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