Selective Endothelin ET_B Receptor Antagonist Improves Left Ventricular Function but Exaggerates Degeneration of Cardiomyocytes in J2N-k Hamsters
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概要
- 論文の詳細を見る
Background Endothelin-1 (ET-1) receptor antagonist is expected to improve the prognosis of patients with heart failure, but the role of the ET_B receptor in cardiac function and structure is complicated. In the present study the NADPH diaphorase activity and ET-1 content in the failing heart treated with ET_A or ET_B receptor antagonist were evaluated in a model of dilated cardiomyopathy. Methods and Results Selective ET_A receptor antagonist, ABT-627 (10mg/kg per day), or selective ET_B antagonist, A-192621 (30mg/kg per day), was given to 22-week-old J2N-k cardiomyopathic hamsters for 8 weeks. The effects of ABT-627 and A-192621 on cardiac function, left ventricular (LV) histology, ET-1 content and NADPH diaphorase activity in the LV were evaluated. Treatment with ABT-627, but not A-192621, significantly decreased ET-1 content and NADPH diaphorase activity. Although the improvement of LV function was modest, ABT-627 prevented tissue damage in J2N-k hamsters. In contrast, A-192621 worsened the degeneration of cardiomyocytes despite improving hemodynamic parameters. Conclusions Selective ET_A antagonist, but not ET_B antagonist, reduced the ET-1 content as well as the NADPH diaphorase activity, and preserved the fine structure of LV myocardium in cardiomyopathic hamsters. Long-term blockade of ET_B receptor might worsen the degeneration of cardiomyocytes through the ET-1/ET_A system even if LV function could be improved.
- 社団法人日本循環器学会の論文
- 2004-12-20
著者
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Yoshiyama M
Department Of Internal Medicine And Cardiology Osaka City University Medical School
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Yamaguchi Junichi
Division Of Cardiology Saitama Prefecture Cardiovascular And Respiratory Center
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Yoshiyama Minoru
Osaka City Univ.
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Hayashi Tetsuya
Third Department of Internal Medicine, Osaka Medical College
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Mori Tatsuhiko
Third Department of Medicine, Osaka Medical College
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MATSUMURA Yasuo
Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences
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Yoshikawa Junichi
Osaka Ekisaikai Hospital
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Hayashi T
Third Dep. Of Medicine Osaka Medical Coll. Jpn
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Hayashi Tetsuya
大阪医科大学 薬理学教室
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Kitaura Yasushi
Third Department Of Internal Medicine Osaka Medical College
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NISHIDA Masahiro
Department of Neurosurgery, Chugoku Rouse Hospital
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Takaoka Masanori
Department Of Internal Medicine Iii Osaka Medical College
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MATSUMURA Yasuo
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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Okada Yoshikatsu
Department of Pathology, Osaka Medical College
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Yoshikawa Junichi
Osaka City University Graduate School Of Medicine
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Ieshima Miyuki
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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Eshiro Keiko
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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Akiyoshi Kenji
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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Eshiro Keiko
Department Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Ieshima Miyuki
Department Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Akiyoshi Kenji
Department Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Hayashi Tetsuya
Third Department Of Medicine Osaka Medical College
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Matsumura Yasuo
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Matsumura Yasuo
Department Of Pharmacology Osaka University Of Phiarmaceutical Sciences
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Matsumura Yasuo
Department Of Mechanical Physics Kyoto University
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Takaoka Masanori
Department Of Electrical And Electronic Engineering University Of Miyazaki
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Matsumura Y
Asahi Glass Co. Ltd. Tokyo Jpn
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Mori Tatsuhiko
Department Of Internal Medicine Iii Osaka Medical College
-
Mori Tatsuhiko
Third Department Of Medicine Osaka Medical College
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Takaoka M
Laboratory Of Pathological And Molecular Pharmacology Osaka University Of Pharmaceutical Sciences
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Okada Yoshikatsu
Department Of Pathology Osaka Medical College
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Nishida Masahiro
Department Of Information And Computer Science Faculty Of Science And Technology Keio University
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Hayashi Tetsuya
Third Department Of Internal Medicine Osaka Medical College
-
Hanafusa Toshiaki
Third Department Of Medicine Osaka Medical College
-
Tanaka Hidekazu
Third Department Of Medicine Osaka Medical College
-
Nishida Masahiro
Department Of Engineering Physics Electronics And Mechanics Graduate School Nagoya Institute Of Tech
-
Nishida Masahiro
Department Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Akiyoshi Kenji
Department Of Cardiovascular Medicine Hokkaido University School Of Medicine
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Mori Tatsuhiko
Third Department of Internal Medicine, Osaka Medical College
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