Beneficial Effects of Angiotensin-Converting Enzyme Inhibition on Sarcoplasmic Reticulum Function in the Failing Heart of the Dahl Rat

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概要

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• Inhibition of angiotensin-converting enzyme (ACE) retards the process of myocardial remodeling and contractile dysfunction that leads to heart failure. However, the intracellular mechanisms by which ACE inhibition preserves myocardial contractility are largely unclear. Using a model of heart failure induced by hypertension in Dahl salt-sensitive (DS) rats, the mechanisms by which ACE inhibitors (ACEI) exert a beneficial effect on myocardial contractility were studied. Dahl salt-resistant (DR) rats, DS rats not given temocapril (DS/T-), and DS rats treated with temocapril (10mg/kg per day from 10 to 17 weeks of age, DS/T+) were fed an 8% NaCl diet from 8 to 17 weeks of age (n=8, each group). Echocardiography, hemodynamic measurement, histology, contraction of isolated skinned papillary muscle, and Western blot analysis were carried out. At an elevated final blood pressure similar to that of the DS/T- rats, DS/T+ rats exhibited (1) a decrease in left ventricular (LV) mass associated with decreases in both cardiomyocyte size and interstitial fibrosis; (2) improvement of both systolic and diastolic LV function; and (3) an increase in caffeine contraction after constant Ca^<2+>-loading with 8-bromo-cAMP into the sarcoplasmic reticulum (SR) associated with an increase in Ser16-phosphorylated phospholamban, as compared with the DS/T- rats. In addition to inhibition of myocardial remodeling, a restoration of the Ca^<2+>- handling ability of the SR by normalized phosphorylated phospholamban may contribute to the improved LV contractile function achieved by chronic treatment with an ACEI.

• 社団法人日本循環器学会の論文
• 2003-07-20

著者

• Kadokami Toshiaki

  Department of Cardiology, Saiseikai Futsukaichi Hospital

• OYAMA Jun-ichi

  Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences

• SUGANO Masahiro

  Department of Cardiovascular, Respiratory and Geriatric Medicine, Kyushu University Hospital at Bepp

• MAKINO Naoki

  Department of Cardiovascular, Respiratory and Geriatric Medicine, Kyushu University Hospital at Bepp

• Suematsu Nobuhiro

  Medical Institute of Bioregulation. Kyushu University

• Sugano Masahiro

  Medical Institute of Bioregulation. Kyushu University

• Makino Naoki

  Medical Institute of Bioregulation. Kyushu University

• Satoh Shinji

  Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University

• Suematsu Nobuhiro

  Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University

• Makino Naoki

  Department Of Cardiovascular Respiratory And Geriatric Medicine Kyushu University Hospital At Beppu

• Makino Naoki

  Division Of Molecular And Clinical Gerontology Medical Inst. Of Bioregulation Kyushu Univ.

• Makino Naoki

  Department Of Bioclimatology And Medicine Medical Institute Of Bioregulation Kyushu University

• Oyama Jun-ichi

  Department Of Cardiovascular Respiratory And Geriatric Medicine Kyushu University Hospital At Beppu

• Oyama Jun-ichi

  Department Of Cardiovascular Medicine Kyushu University Graduate School Of Medical Sciences

• Kadokami Toshiaki

  Department Of Bioclimatology And Medicine Medical Institute Of Bioregulation Kyushu University

• Makino Naoki

  Division Of Molecular And Clinical Gerontology Department Of Molecular And Cellular Biology Medical

• Sugano Masahiro

  Division Of Molecular And Clinical Gerontology Department Of Molecular And Cellular Biology Medical

• Sugano Masahiro

  Department Of Cardiovascular Respiratory And Geriatric Medicine Kyushu University Hospital At Beppu

• Satoh Shinji

  Division Of Cardiology National Hospital Organization Kyushu Medical Center

• Ueda Yasuko

  Division Of Molecular And Clinical Gerontology Medical Institute Of Bioregulation Kyushu University

• Satoh Shinji

  Medical Institute Of Bioregulation. Kyushu University

• YOSHIKAWA Yasuji

  Diagnostic Laboratory, Medical Institute of Bioregulation, Kyushu University

• Makino Naoki

  Departent Of Bioclimatology And Medicine Medical Institute Of Bioregulation Kyushu University

• Sugano Masahiro

  Division Of Molecular And Clinical Gerontology Medical Inst. Of Bioregulation Kyushu Univ.

• Ueda Yasuko

  Department of Bioclimatology and Medicine, Medical Institute of Bioregulation, Kyushu University

• Yoshikawa Yasuji

  Diagnostic Laboratory Medical Institute Of Bioregulation Kyushu University

• Sugano Masahiro

  Department Of Molecular And Cellular Biology Division Of Molecular And Clinical Gerontology Medical

• Makino Naoki

  Department Of Molecular And Cellular Biology Division Of Molecular And Clinical Gerontology Medical

• Sugano Masahiro

  Department Of Cardiovascular Respiratory And Geriatric Medicine Kyushu University Hospital At Beppu

• Sato Shinji

  Division Of Molecular And Clinical Gerontology Medical Inst. Of Bioregulation Kyushu Univ.

• Oyama Junichi

  Department Of Molecular And Cellular Biology Division Of Molecular And Clinical Gerontology Medical

• Sugano Masahiro

  Department Of Bioclimatology And Medicine Medical Institute Of Bioregulation Kyushu University

• Satoh Shinji

  Department Of Bioclimatology And Medicine Medical Institute Of Bioregulation Kyushu University

• Sato Shinji

  Department Of Molecular And Cellular Biology Division Of Molecular And Clinical Gerontology Medical Institute Of Bioregulation Kyushu University

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