Serial Alterations of β-Adrenergic Signaling in Dilated Cardiomyopathic Hamsters : Possible Role of Myocardial Oxidative Stress

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• Background The relationship between enhanced myocardial oxidative stress and impaired β-adrenergic signaling remains to be characterized during the development of dilated cardiomyopathy. Methods and Results Alterations in myocardial oxidative stress and β-adrenergic signaling, as well as left ventricular (LV) functional and structural changes, were evaluated during the development of cardiomyopathy in TO-2 hamsters; F1B hamsters served as controls. LV dysfunction was first apparent at 8 weeks of age and deteriorated thereafter in the TO-2 hamsters. At 32 weeks, the animals exhibited heart failure with an increased plasma norepinephrine concentration. Cardiac myolysis, as demonstrated by elevated plasma concentration of cardiac troponin T, peaked at 8 weeks. The glutathione redox ratio revealed increased oxidative stress in the LV myocardium in TO-2 hamsters even at 4 weeks and became manifest after 8 weeks. The hearts of TO-2 hamsters had significantly reduced superoxide dismutase activity from 8 weeks onward compared with control hamsters. However, glutathione peroxidase activity was unchanged at any time point. The LV functional response to isoproterenol was markedly reduced at 8 weeks, without any apparent changes in the amount of β-adrenergic signaling molecules, and it deteriorated thereafter. Adenylyl cyclase activity was significantly decreased, despite increased amounts of both Gsa mRNA and protein, in the LV myocardium at 18 weeks. Conclusions Myocardial oxidative stress is actually enhanced in the initial development of LV dysfunction. Both activation of myocardial oxidative stress and impairment of β-adrenergic signaling become prominent at the stage of severe LV dysfunction. Myocardial oxidative stress may be involved in the development of β-adrenergic desensitization.

• 社団法人日本循環器学会の論文
• 2004-10-20

著者

• Ichihara Gaku

  Dep. Of Occupational And Environmental Health Graduate School Of Medicine Nagoya Univ.

• Kimata Hirotaka

  Department Of Cardiology Nagoya University School Of Medicine

• Kanazawa Hiroaki

  Department Of Pathobiological Science And Technology Faculty Of Medicine Tottori University

• Watarai Masato

  School Of Health Sciences Nagoya University School Of Medicine

• Nagata Kohzo

  Department of Medical Technology, Nagoya University School of Health Sciences

• Kimata Hirotaka

  Department Of Pathobiological Science And Technology Faculty Of Medicine Tottori University

• Moriyama T

  Osaka Univ. Osaka Jpn

• Nagata Kohzo

  名古屋大学 医学系研究科病態解析学

• Nagata Kohzo

  名古屋大学 医学系研究科循環器ゲノム情報応用診断学

• Watanabe Makoto

  Anjo Kosei Hospital

• Obata Koji

  Department of Phamacology, Achigakuin University School of Dentistry

• Iwase Mitsunori

  Division of Integrated Medicine, Toyota Memorial Hospital

• KITAICHI Kiyoyuki

  Nagoya University School of Health Sciences

• Yokota Mitsuhiro

  Department Of Genome Science School Of Dentistry Aichi-gakuin University

• Yokota Mitsuhiro

  Department Of Clinical Pathophysiology Nagoya University Graduate School Of Medicine

• Obata Koji

  名古屋大学 循環器内科

• Kanda Hirofumi

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Nishizawa Takao

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Kondo Kazuhisa

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Nakamura Kae

  名古屋大学 循環病態探索医療学

• Iwase M

  Pathophysiological Laboratory Sciences Graduate School Of Medicine Nagoya University

• KANDA Hirofumi

  First Department of Internal Medicine

• Mizuno Tomofumi

  愛知医科大学 循環器内科

• Ichihara Gaku

  Occupational And Environmental Health Nagoya University Graduate School Of Medicine

• Kanazawa Hiroaki

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Iwase Mitsunori

  名古屋大学 医学系研究科医療技術科学専攻

• Ichihara Sahoko

  Mie University School of Medicine

• Yokoi Toyoharu

  Nagoya University School of Health Sciences

• Watanabe Masato

  Daiichi Radio-isotope Laboratories

• Tsunematsu Takashi

  Yokohama City University Schoolof Medicine

• Ishikawa Yoshihiro

  Yokohama City University Schoolof Medicine

• Murohara Toyoaki

  Cardiology, Nagoya University Graduate School of Medicine

• Iwase Mitsunori

  Division Of Acute Coronary Syndrome Aichi Council Of Advanced Emergency Care

• Iwase Mitsunori

  School Of Health Sciences Nagoya University

• Obata Koji

  Department Of Information Engineering Nagoya University

• Nagata Kohzo

  Department Of Medical Technology Nagoya University School Of Health Sciences

• Kanda Hirofumi

  Department Of Pathobiological Science And Technology Faculty Of Medicine Tottori University

• Matsubara Tatsuaki

  Internal Medicine School Of Dentistry Aichi-gakuin University

• Yokota Mitsuhiro

  Division Of Cardiology Gifu Social-insurance Hospital

• Iwase Mitsunori

  Pathophysiological Laboratory Sciences Graduate School Of Medicine Nagoya University

• Kobayashi Koichi

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Yokota Mitsuhiro

  Department Clinical Laboratory Nagoya University Hospital

• Kanda Hirofumi

  Department Of Cardiology Nagoya University School Of Medicine

• Ichihara Sahoko

  Cardiovascular Division Department Of Pathophysiology Nagoya University Graduate School Of Medicine

• Kaibuchi Kozo

  Department Of Molecular Pharmacology Nagoya University Graduate School Of Medicine

• Iwase Masatsugu

  Division Of Integrated Medicine Toyota Memorial Hospital

• Iwase Mitsunori

  Department Of Medical Technology Nagoya University School Of Health Sciences

• Yokota Mitsuhiro

  Nagoya University College Of Medical Technology Cardiovascular Section Department Of Clinical Labora

• Kanazawa Hiroaki

  Department Of Anatomy Niigata University School Of Medicine

• Watanabe Masato

  School Of Health Sciences Nagoya University School Of Medicine

• Okumura Kenji

  2nd Department Of Internal Medicine Nagoya University School Of Medicine Nagoya.

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