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Effect of Cilazapril on Ventricular Remodeling Assessed by Doppler-Echocardiographic Assessment and Cardiac Gene Expression

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Abstract

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 ± 3% vs. MI, 17 ± 3%; P <0.01) and ejection fraction measured by the modified Simpson’s method (control, 61 ± 2% vs. MI, 36 ± 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in β-MHC, α-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca2+-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.

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Authors and Affiliations

  1. First Department of Internal Medicine, Japan

    Minoru Yoshiyama, Kazuhide Takeuchi, Akihisa Hanatani, Takehiro Shimada, Yasuhiko Takemoto, Naruhito Shimizu, Takashi Omura & Junichi Yoshikawa

  2. Department of Pharmacology, Osaka City University Medical School, Osaka, Japan

    Shokei Kim & Hiroshi Iwao

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  1. Minoru Yoshiyama
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  2. Kazuhide Takeuchi
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  3. Akihisa Hanatani
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  4. Takehiro Shimada
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  5. Yasuhiko Takemoto
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  8. Shokei Kim
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Yoshiyama, M., Takeuchi, K., Hanatani, A. et al. Effect of Cilazapril on Ventricular Remodeling Assessed by Doppler-Echocardiographic Assessment and Cardiac Gene Expression. Cardiovasc Drugs Ther 12, 57–70 (1998). https://doi.org/10.1023/A:1007789519005

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