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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概要
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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.
著者
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Yamawaki Hideyuki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
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Okada Muneyoshi
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
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Hara Yukio
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
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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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Okada Muneyoshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Okada Muneyoshi
Department Of Veterinary Pharmacology School Of Veterinary Medicine And Animal Sciences Kitasato Uni
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Okada Muneyoshi
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
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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YAMAWAKI Hideyuki
Laboratory of Veterinary Pharmacology, Kitasato University, Towada, Aomori 034–8628, Japan
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HARA Yukio
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University
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