Characteristic Effects of α1-β_1,2-Adrenergic Blocking Agent, Carvedilol, on [Ca^2+]_i in Ventricular Myocytes Compared With Those of Timolol and Atenolol
スポンサーリンク
概要
- 論文の詳細を見る
Beta-adrenergic stimulation and the resultant Ca^2+ load both seem to be associated with progression of heart failure as well as hypertrophy. Because the α1-, β1,2-blocker, carvedilol, has been shown to be outstandingly beneficial in the treatment of heart failure, its direct effects on intracellular calcium ion concentration ([Ca^2+]_i), including antagonism to isoproterenol, in ventricular myocytes were investigated and then comapred with a selective β1-blocker, atenolol, and a non-selective β1,2-blocker, timolol. At 1-300 nmol/L, carvedilol decreased the amplitude of [Ca^2+]_i by〜20% independently of its concentration, which was a similar effect to timolol. All the β-blockers at lOnmol/L decreased the amount of cAMP, but atenolol had the least effect. Carvedilol in the ,umol/L order further diminished the amplitude of [Ca^2+]_i transients, and at 10μmol/L increased the voltage threshold for pacing myocytes. These effects were not observed with timolol or atenolol. L-type Ca^2+ currents (ICa) were decreased by carvedilol in the ,μmol/L order in a concentration dependent manner. As for the β-antagonizing effect, the concentrations of carvedilol, timolol, and atenolol needed to prevent the effect of isoproterenol by 50% (IC_50) were 1.32, 2.01, and 612nmol/L, respectively. Furthermore, the antagonizing effect of carvedilol was dramatically sustained even after removal of the drug from the perfusate. Carvedilol exerts negative effects on [Ca^2+]_i, including inhibition of the intrinsic β-activity, reduction of ICa in the μmol/L order, and an increase in the threshold for pacing at >10μmol/L. Data on the IC_50 for the isoproterenol effect suggest that carvedilol could effectively inhibit the [Ca^2+]_i load induced by catecholamines under clinical conditions.
- 社団法人日本循環器学会の論文
- 2002-12-20
著者
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NAGAI Ryozo
Department of Cardiovascular Medicine, University of Tokyo
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Komuro Issei
Department of Cardiovascular Science and Medicine, Chiba University graduate School of Medicine
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Takahashi Toshiyuki
Department of Cardiology, JR Tokyo General Hospital
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Takahashi Toshiyuki
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Harada Kazumasa
Department of Cardiology, Tokyo Metropolitan Geriatric Hospital
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Harada Kazumasa
Tokyo Metropolitan Geriatric Hospital Department Of Cardiology
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MATSUO Hiroshi
Second Department of Internal Medicine,University of Tokyo
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Oyama Tomomi
Department Of Cardiovascular Science And Medicine Chiba University School Of Medicine
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Oyama Tomomi
Department Of Cardiovascular Medicine University Of Tokyo Graduate School Of Medicine
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Yao Atsushi
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine
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MARUYAMA Takashi
Department of Surgery, Funabashi Municipal Medical Center
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Kohmoto Osami
Second Department of Internal Medicine
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Sugishita Yasuyuki
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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Shimizu Tatsuya
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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Matsui Hiroshi
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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Serizawa Takashi
Second Department of Internal Medicine
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Kohmoto Osami
The Second Department of Medicine, Saitama Medical School
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Harada Kazumasa
Department Of Cardiology Tokyo Metropolitan Geriatric Hospital
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Kohmoto Osami
The Second Department Of Medicine Saitama Medical School
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Komuro Issei
Department Of Cardiovascular Medicine Chiba University School Of Medicine
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Sugishita Yasuyuki
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Yao Atsushi
Department Of Cardiovascular Medicine Graduate School Of Medicine The University Of Tokyo
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Yao Atsushi
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Kohmoto Osami
The Second Department Of Internal Medicine Faculty Of Medicine University Of Tokyo
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Takahashi Tomiko
Department Of Cardiovascular Medicine University Of Tokyo
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Nagai Ryozo
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Takahashi Toshiyuki
Department Of Cardiovascular Medicine University Of Tokyo Graduate School Of Medicine
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Yao Atsushi
Department Of Cardiovascular Medicine The University Of Tokyo Hospital
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Matsui Hiroshi
Research Institute National Center Of Cardiovascular Medicine
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Nagai Ryouzou
The Department Of Cardiovascular Diseases Graduate School Of Medicine University Of Tokyo
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Shimizu Tatsuya
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Takahashi Tomiko
Department Of Laboratory Medicine University Of Tokyo
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Takahashi Toshiyuki
Department Of Biology Keio University
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Takahashi Toshiyuki
Department Of Cardiovascular Medicine University Of Tokyo
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Toshimori Tsukasa
2nd Dept. Of Biochem. Miyazaki Med. Coll.
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Nagai Ryozo
Department Of Cardiology Kitano Hospital Medical Research Institute
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Yao Atsushi
Department Of Cardiology Tokyo University Hospital
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Matsuo Hiroshi
Second Department Of Internal Medicine Saitama Medical School
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Maruyama Takashi
Department Of Surgery Funabashi Municipal Medical Center
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Takahashi Toshiyuki
Department Of Biological Science Graduate School Of Science Hiroshima University
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Nagai Ryozo
Department Cardiovascular Medicine The University Of Tokyo Hospital
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Shimizu Tatsuya
Department Of Cardiology Jr Tokyo General Hospital
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Takahashi Toshiyuki
The 2nd Department Of Internal Medicine University Of Tokyo
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Takahashi Toshiyuki
Department Of Cardiovascular Medicine Tokyo Graduate School Of Medicine
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Maruyama Takashi
Department Of Pharmacology Saitama Medical University
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Maruyama Takashi
Department Of Cardiovascular Surgery Hokkaido University School Of Medicine:department Of Pharmacolo
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Sugishita Yasuyuki
Department Of Cardiology Kanto Central Hospital
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Shimizu Tatsuya
Department Of Biochemistry And Molecular Biology Nippon Medical School
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Takahashi Toshiyuki
Department Of Dermatology Faculty Of Medicine University Of Tokyo
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Komuro Issei
Department Of Cardiovascular Medicine
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Takahashi Toshiyuki
Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University
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