2017年
Suppressive Effect of Carvedilol on Na+/Ca2+ Exchange Current in Isolated Guinea-Pig Cardiac Ventricular Myocytes
PHARMACOLOGY
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 99
- 号
- 1-2
- 開始ページ
- 40
- 終了ページ
- 47
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1159/000450753
- 出版者・発行元
- KARGER
Background and Aims: Carvedilol ((+/)-1-(carbazol4-yloxy)-34[2-(o-nnethoxyphenoxy)ethyliannino]-2-propa- nol), a beta-adrenoceptor-blocker, has multi-channel blocking and vasodilator properties. This agent dose-dependently improves left ventricular function and reduces mortality in patients with arrhythmia and chronic heart failure. However, the effect of carvedilol on the cardiac Na+/Ca2+ exchanger (NCX1) has not been investigated. Methods and Results: We examined the effects of carvedilol and metoprolol, 2 beta-blockers, on Na+/Ca2+ exchange current (I-NCX) in guineapig cardiac ventricular cells and fibroblasts expressing dog cardiac NCX1. Carvedilol suppressed INcx in a concentration dependent manner but metoprolol did not. IC50 values for the Ca2+ influx (outward) and efflux (inward) components of INcx were 69.7 and 61.5 mu mol/l, respectively. Carvedilol at 100 mu mol/l inhibited I-NCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 mu mol/l abolished ouabain-induced delayed afterdepolarizations. Conclusion: Carvedilol inhibited cardiac NCX in a concentration-dependent manner in isolated cardiac ventricles, but metoprolol did not. We conclude that carvedilol inhibits NCX1 at supratherapeutic concentrations. (C) 2016 S. Karger AG, Basel
- リンク情報
- ID情報
-
- DOI : 10.1159/000450753
- ISSN : 0031-7012
- eISSN : 1423-0313
- PubMed ID : 27673688
- Web of Science ID : WOS:000393268700005