Spironolactone decreases isoproterenol-induced ventricular fibrosis and matrix metalloproteinase-2 in rats.
Biol Pharm Bull
; 34(1): 61-5, 2011.
Article
em En
| MEDLINE
| ID: mdl-21212518
ABSTRACT
Although transregulation between the sympathetic nervous system and the renin-angiotensin-aldosterone system has been reported, it remains unclear whether sympathetic hyperactivity-induced matrix metalloproteinease (MMP) expression/activity and cardiac fibrosis are mediated by the mineralocorticoid receptor system. We investigated whether isoproterenol (ISO)-induced MMP expression/activity and cardiac fibrosis are mediated by spironolactone in rats. Male Wistar Kyoto rats were divided into 3 groups control, ISO, and ISO combined with spironolactone (SPI). ISO (2.0 mg/kg/d) and/or SPI (40 mg/kg/d) were given for 14 d. Echocardiography and hemodynamic measurements were recorded and hearts were excised. The myocyte cross-sectional and fibrotic area was evaluated via histopathological analysis. MMP-2 and collagen-I were analyzed by Western blotting and zymography. Compared with the controls, ISO significantly elevated the end-diastolic left ventricular (LV) pressure and the time constant of isovolumic relaxation and decreased the -dP/dt, while those of SPI co-treatment did not. ISO treatment induced significant increases in the fractional shortening and relative wall thickness, whereas SPI co-treatment significantly decreased relative wall thickness. Similarly, ISO significantly increased LV weight and myocyte cross-sectional and fibrotic area, which occurred concomitantly with the MMP-2 expression/activity and the expression of collagen-I. Moreover, ISO induced these features were significantly attenuated by SPI co-treatment. Our results suggest that ISO-evoked sympathetic hyperactivity induced LV fibrosis and MMP-2, which may be partially controlled via the mineralocorticoid receptor system.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espironolactona
/
Fibrose
/
Metaloproteinase 2 da Matriz
/
Cardiopatias
/
Isoproterenol
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article