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Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of SGK-1.
MedLine Citation:
PMID:  22327331     Owner:  NLM     Status:  Publisher    
Rationale: Persistent β-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. Objective: To study the cardiac effects of the mineralocorticoid receptor antagonist spironolactone, on response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in heart.Methods and Results: Male Wistar rats received isoproterenol (3mg/kg/day) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200mg/kg/day). 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, which were normalized by spironolactone treatment. mRNA levels of transforming growth factor beta, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumor necrosis factor alpha, interleukin 1beta, p22phox and xanthine dehydrogenase were increased (p<0.05) in isoproterenol-treated rats and prevented by spironolactone (p<0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. Conclusion: 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 cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction, induced by isoproterenol treatment in rats.
Beatriz Martín-Fernández; Natalia de Las Heras; María Miana; Sandra Ballesteros; María Valero-Muñoz; Dalton Vassallo; Ana Paula Davel; Luciana Venturini Rossoni; Victoria Cachofeiro; Vicente Lahera
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-10
Journal Detail:
Title:  Experimental physiology     Volume:  -     ISSN:  1469-445X     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Department of Physiology, School of Medicine. Universidad Complutense. Madrid, Spain;
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