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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\u20101, in the heart. Male Wistar rats received isoproterenol (3 mg kg<jats:sup>\u22121<\/jats:sup>day<jats:sup>\u22121<\/jats:sup>) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg<jats:sup>\u22121<\/jats:sup>day<jats:sup>\u22121<\/jats:sup>). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end\u2010diastolic pressure observed in isoproterenol\u2010treated 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 \u03b2, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor \u03b1, interleukin 1\u03b2, p22phox and xanthine dehydrogenase were increased (<jats:italic>P<\/jats:italic>&lt; 0.05) in isoproterenol\u2010treated rats, and this effect was prevented by spironolactone (<jats:italic>P<\/jats:italic>&lt; 0.05). Spironolactone also reduced the elevated SGK\u20101 expression in isoproterenol\u2010treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK\u20101, by spironolactone in hearts from isoproterenol\u2010treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.<\/jats:p>","DOI":"10.1113\/expphysiol.2011.063230","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T05:00:19Z","timestamp":1328936419000},"page":"710-718","source":"Crossref","is-referenced-by-count":18,"title":["Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum\u2010 and glucocorticoid\u2010regulated kinase type 1"],"prefix":"10.1113","volume":"97","author":[{"given":"Beatriz","family":"Mart\u00edn\u2010Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"de las 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