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Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after Myocarditis

  • Wen Juan
  • Mikio Nakazawa
  • Kenichi Watanabe
  • Meilei Ma
  • Mir I. I. Wahed
  • Go Hasegawa
  • Makoto Naito
  • Tadashi Yamamoto
  • Koichi Fuse
  • Kiminori Kato
  • Makoto Kodama
  • Yoshifusa Aizawa
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 43)

Abstract

The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), ±dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-β1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and ±dP/dt was lower in V (14.1 ± 2.0 mmHg and +2409 ± 150/−2318 ± 235 mmHg/sec) than in age-matched normal rats (5.0 ± 0.6 mmHg and +6173 ± 191/−7120 ± 74 mmHg/sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and ±dP/dt was increased in a dose-dependent manner (10.8 ± 1.8 mmHg and +3211 ± 307/−2928 ± 390 mmHg/sec in Q0.2, 9.4 ± 1.5 mmHg and +2871 ± 270/−2966 ± 366 mmHg/sec in Q2, and 6.6 ± 1.5 mmHg, and +3569 ± 169/−3960 ± 203 mmHg/sec in Q20). Increased expression levels of TGF-β1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril.

Keywords

angiotensin-converting enzyme inhibitor dilated cardiomyopathy collagen heart failure fibrosis quinapril 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Wen Juan
    • 1
  • Mikio Nakazawa
    • 2
  • Kenichi Watanabe
    • 1
    • 6
  • Meilei Ma
    • 1
  • Mir I. I. Wahed
    • 1
  • Go Hasegawa
    • 3
  • Makoto Naito
    • 3
  • Tadashi Yamamoto
    • 4
  • Koichi Fuse
    • 5
  • Kiminori Kato
    • 5
  • Makoto Kodama
    • 5
  • Yoshifusa Aizawa
    • 5
  1. 1.Department of Clinical PharmacologyNiigata University of Pharmacy and Applied Life SciencesNiigataJapan
  2. 2.Department of Medical Technology, School of Health Sciences, Faculty of MedicineNiigata UniversityNiigataJapan
  3. 3.Second Department of PathologyNiigata UniversityNiigataJapan
  4. 4.Department of Structural Pathology, Institute of NephrologyNiigata UniversityNiigataJapan
  5. 5.First Department of Medicine, School of Medicine, Faculty of MedicineNiigata UniversityNiigataJapan
  6. 6.Department of Clinical PharmacologyNiigata College of PharmacyNiigataJapan

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