Characteristic Effects of .ALPHA.1-.BETA.1,2-Adrenergic Blocking Agent, Carvedilol, on [Ca2+]i in Ventricular Myocytes Compared With Those of Timolol and Atenolol.
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- Yao Atsushi
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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- Kohmoto Osami
- Second Department of Internal Medicine
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- Oyama Tomomi
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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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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- Harada Kazumasa
- 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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- Komuro Issei
- Department of Cardiovascular Medicine, Graduate School of 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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- Matsuo Hiroshi
- Second Department of Internal Medicine
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- Serizawa Takashi
- Second Department of Internal Medicine
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- Maruyama Takashi
- Department of Pharmacology, Saitama Medical University
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- Takahashi Toshiyuki
- Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
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抄録
Beta-adrenergic stimulation and the resultant Ca2+ 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 ([Ca2+]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 [Ca2+] i by ~20% independently of its concentration, which was a similar effect to timolol. All the β-blockers at 10 nmol/L decreased the amount of cAMP, but atenolol had the least effect. Carvedilol in the μmol/L order further diminished the amplitude of [Ca2+]i transients, and at 10 μmol/L increased the voltage threshold for pacing myocytes. These effects were not observed with timolol or atenolol. L-type Ca2+ 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% (IC50) were 1.32, 2.01, and 612 nmol/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 [Ca2+]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 ≥10 μmol/L. Data on the IC50 for the isoproterenol effect suggest that carvedilol could effectively inhibit the [Ca2+]i load induced by catecholamines under clinical conditions. (Circ J 2003; 67: 83 - 90)<br>
収録刊行物
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- Circulation Journal
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Circulation Journal 67 (1), 83-90, 2003
一般社団法人 日本循環器学会
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詳細情報 詳細情報について
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- CRID
- 1390001205104089216
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- NII論文ID
- 110002666214
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- NII書誌ID
- AA11591968
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- COI
- 1:CAS:528:DC%2BD3sXlt1Sksw%3D%3D
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- ISSN
- 13474820
- 13469843
- http://id.crossref.org/issn/13469843
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- PubMed
- 12520158
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- 使用不可