Mechanisms of Combined Treatment With Celiprolol and Candesartan for Ventricular Remodeling in Experimental Heart Failure
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概要
- 論文の詳細を見る
Background Both β-adrenergic blockers and angiotensin-II receptor blockers were reported to improve the prognosis of patients with heart failure, but the efficacy of combination therapy with these agents has not been fully elucidated. Also the efficacy of celiprolol, a β_1-selective adrenoceptor antagonist with partial β_2-agonist properties, for heart failure treatment is still controversial. We examined the cardioprotective effects and mechanisms of the therapy with celiprolol or candesartan, an angiotensin-II receptor blockers and their combination in heart failure induced by isoproterenol (ISO). Methods and Results ISO 300mg/kg was injected in rats to produce heart failure. Two months after the injection, the ISO-injected rats were divided into 4 groups (8 rats each) and treated for 4 weeks as follows : (a) vehicle ; (b) celiprolol 10mg/kg per day (BB); (c) candesartan 0.2mg/kg per day (ARB) ; and (d) their combination BB+ARB. ISO significantly elevated left ventricular (LV) end-diastolic pressure, decreased peak-negative dP/dt and LV ejection fraction. BB and ARB similarly ameliorated cardiac dysfunction due to ISO, but BB+ARB were more potent than the individual therapies. Separately, ARB preserved the histological structure in LV myocardium. In contrast, BB ameliorated calcium handling, as shown by the increased ratio of SERCA2 to phospholamban protein, despite having little effect on the histology. Conclusion Both celiprolol and candesartan showed cardioprotective effects in this heart failure model. The potential use of the combination treatment in heart failure might result in a synergistic effect through the different cardioprotective mechanisms of celiprolol and candesartan.
- 社団法人日本循環器学会の論文
- 2005-04-20
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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SOHMIYA Koichi
Third Department of Internal Medicine, Osaka Medical College
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Okuda Nobuaki
Third Department of Internal Medicine, Osaka Medical College
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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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Okuda Nobuaki
The Third Department Of Internal Medicine Osaka Medical College
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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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Kudoh Sumiyo
Department Of Internal Medicine Iii Osaka Medical College
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Sohmiya Koichi
Department Of Internal Medicine Iii Osaka Medical College
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Sohmiya Koichi
Third Department Of Internal Medicine Osaka Medical College
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Shimomura Hiroaki
Third Division, Department of Internal Medicine, Osaka Medical College
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Kitaura Yasushi
Third Department Of Internal Medicine Osaka Medical College
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Takaoka Masanori
Department Of Internal Medicine Iii Osaka Medical College
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Ohkita Mamoru
Osaka University Of Pharmaceutical Science
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Matsumura Yasuo
Osaka University of Pharmaceutical Sciences Osaka Medical College
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Yoshikawa Junichi
Osaka City University Graduate School Of Medicine
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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
Osaka University Of Pharmaceutical Sciences
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Shimomura Hiroaki
Third Department Of Internal Medicine Osaka Medical College
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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
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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
-
Okuda Nobuaki
Third Department Of Internal Medicine Osaka Medical College
-
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
-
Mori Tatsuhiko
Department Of Gastroenterology And Neurology Faculty Of Medicine Kagawa University
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Mori Tatsuhiko
Third Department of Internal Medicine, Osaka Medical College
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