Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats
Little is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old...
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Elsevier
2008-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319313222 |
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| author | Muneyoshi Okada Ryuta Kikuzuki Toshiyuki Harada Yasutomo Hori Hideyuki Yamawaki Yukio Hara |
| author_facet | Muneyoshi Okada Ryuta Kikuzuki Toshiyuki Harada Yasutomo Hori Hideyuki Yamawaki Yukio Hara |
| author_sort | Muneyoshi Okada |
| collection | DOAJ |
| description | Little is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old male Wistar rats were injected intraperitoneally with monocrotaline (60 mg/kg) or saline. The rats were administrated captopril (30 mg/kg per day) or a vehicle orally for 24 days from the day of monocrotaline injection. At day 25, echocardiography was performed and hearts were excised. Expressions and activities of MMP-2 and MMP-9 were measured by Western blotting and by gelatin zymography, respectively. In monocrotaline-injected rats, right ventricular weight/tail length ratio increased significantly. Histological analysis revealed cardiomyocyte hypertrophy and fibrosis in right ventricular sections. Echocardiography showed right ventricular dysfunction compared with saline-injected rats. The right ventricular hypertrophy, fibrosis, and dysfunction were inhibited by captopril. However, captopril did not attenuate an increase in pulmonary artery pressure. MMP-2 and MMP-9 expressions and activities in right ventricles increased significantly in monocrotaline-injected rats and captopril inhibited them. These findings indicate that captopril attenuates the development of monocrotaline-induced right ventricular hypertrophy in association with inhibition of MMP-2 and MMP-9 in rats. Keywords:: angiotensin-converting enzyme inhibitor, captopril, matrix metalloproteinase, monocrotaline, right ventricular hypertrophy |
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| issn | 1347-8613 |
| language | English |
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| publishDate | 2008-01-01 |
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| spelling | doaj.art-655146ea44504c829a4b29c87efe98222022-12-21T17:16:51ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011084487494Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in RatsMuneyoshi Okada0Ryuta Kikuzuki1Toshiyuki Harada2Yasutomo Hori3Hideyuki Yamawaki4Yukio Hara5Laboratories of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Corresponding author. mokada@vmas.kitasato-u.ac.jpLaboratories of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanLaboratories of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanLaboratories of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanLaboratories of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanLaboratories of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanLittle is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old male Wistar rats were injected intraperitoneally with monocrotaline (60 mg/kg) or saline. The rats were administrated captopril (30 mg/kg per day) or a vehicle orally for 24 days from the day of monocrotaline injection. At day 25, echocardiography was performed and hearts were excised. Expressions and activities of MMP-2 and MMP-9 were measured by Western blotting and by gelatin zymography, respectively. In monocrotaline-injected rats, right ventricular weight/tail length ratio increased significantly. Histological analysis revealed cardiomyocyte hypertrophy and fibrosis in right ventricular sections. Echocardiography showed right ventricular dysfunction compared with saline-injected rats. The right ventricular hypertrophy, fibrosis, and dysfunction were inhibited by captopril. However, captopril did not attenuate an increase in pulmonary artery pressure. MMP-2 and MMP-9 expressions and activities in right ventricles increased significantly in monocrotaline-injected rats and captopril inhibited them. These findings indicate that captopril attenuates the development of monocrotaline-induced right ventricular hypertrophy in association with inhibition of MMP-2 and MMP-9 in rats. Keywords:: angiotensin-converting enzyme inhibitor, captopril, matrix metalloproteinase, monocrotaline, right ventricular hypertrophyhttp://www.sciencedirect.com/science/article/pii/S1347861319313222 |
| spellingShingle | Muneyoshi Okada Ryuta Kikuzuki Toshiyuki Harada Yasutomo Hori Hideyuki Yamawaki Yukio Hara Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats Journal of Pharmacological Sciences |
| title | Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats |
| title_full | Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats |
| title_fullStr | Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats |
| title_full_unstemmed | Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats |
| title_short | Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats |
| title_sort | captopril attenuates matrix metalloproteinase 2 and 9 in monocrotaline induced right ventricular hypertrophy in rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319313222 |
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