Spironolactone Decreases Isoproterenol-Induced Ventricular Fibrosis and Matrix Metalloproteinase-2 in Rats
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- Hori Yasutomo
- Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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- Yoshioka Kazuki
- Laboratory of Veterinary Anatomy, School of Veterinary Medicine, Kitasato University
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- Kanai Kazutaka
- Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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- Hoshi Fumio
- Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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- Itoh Naoyuki
- Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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- Higuchi Sei-ichi
- Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University
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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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (1), 61-65, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204626040448
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- NII論文ID
- 130000402263
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 10926748
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- 使用不可