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标题：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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作者：Muneyoshi Okada ; Natsuko Kosaka ; Yoshikazu Hoshino 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：9
页码：1517-1521
DOI：10.1248/bpb.33.1517
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：matrix metalloproteinase;myocardial fibrosis;isoprenaline;angiotensin converting enzyme inhibitor;angiotensin II type 1 receptor antagonist