Effects of Captopril and Telmisartan on Matrix Metalloproteinase-2 and -9 Expressions and Development of Left Ventricular Fibrosis Induced by Isoprenaline in Rats
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- Okada Muneyoshi
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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- Kosaka Natsuko
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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- Hoshino Yoshikazu
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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- Yamawaki Hideyuki
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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- Hara Yukio
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
Bibliographic Information
- Other Title
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- Highlighted paper selected by editor-in-chief: Effects of captopril and telmisartan on matrix metalloproteinase-2 and -9 expressions and development of left ventricular fibrosis induced by isoprenaline in rats
- Effects of captopril and telmisartan on matrix metalloproteinase-2 and −9 expressions and development of left ventricular fibrosis induced by isoprenaline in rats
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Abstract
The aim of this study was to clarify the effects of renin-angiotensin system (RAS) blockade by captopril, an angiotensin converting enzyme inhibitor, and telmisartan, an angiotensin II type 1 receptor antagonist, on matrix metalloproteinase (MMP)-2 and MMP-9 expressions and development of left ventricular (LV) fibrosis induced by isoprenaline in rats. Rats were treated with subcutaneous injection of isoprenaline (5 mg/kg/d) and with oral administration of captopril (30 mg/kg/d) or telmisartan (3 mg/kg/d) for 1 or 7 d. Hearts were excised at the day 2 and day 8. Degree of fibrosis was evaluated by Azan staining. MMP-2 and MMP-9 expressions were analyzed by Western blotting. Localization of MMP-9 expression in LV section was detected by immunohistochemical staining. At the day 8, myocardial fibrosis was observed in LV section from isoprenaline-treated rats. Captopril but not telmisartan significantly enhanced the isoprenaline-induced myocardial fibrosis. MMP-9 expression at the day 2 and MMP-2 expression at the day 8 increased significantly in LV from isoprenaline-treated rats. Captopril had no influence on the MMP-2 expression, but significantly augmented the isoprenaline-induced MMP-9 expression. Telmisartan had no effect on the isoprenaline-induced MMP-2 and MMP-9 expressions. In immunohistochemical staining, MMP-9 positive-interstitial cells were extensively observed in LV sections from isoprenaline + captopril-treated rats at the day 2. The present study reveals that RAS blockade by captopril and telmisartan does not have suppressive effects on isoprenaline-induced MMP-2 and MMP-9 expressions as well as LV fibrosis. Furthermore, captopril may enhance LV fibrosis through promoting isoprenaline-induced MMP-9 expression in cardiac interstitial cells.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 33 (9), 1517-1521, 2010
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679603277824
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- NII Article ID
- 130000322349
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 10796825
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed