Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

DOI Web Site 被引用文献10件 参考文献58件
  • Okada Muneyoshi
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
  • Kikuzuki Ryuta
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
  • Harada Toshiyuki
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
  • Hori Yasutomo
    Laboratory of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, Japan
  • Yamawaki Hideyuki
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan
  • Hara Yukio
    Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan

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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.<br>

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