Suppressive Effect of Carvedilol on Na+/Ca2+ Exchange Current in Isolated Guinea-Pig Cardiac Ventricular Myocytes
| Autor: | Junko Kimura, Yasuhide Watanabe, Takahiro Iwamoto, Miyuki Tashiro, Kanna Yamashita, Satomi Kita, Tomomi Yamakawa |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
medicine.medical_specialty Sodium-calcium exchanger Chemistry General Medicine 030204 cardiovascular system & hematology Adrenergic beta-Antagonists Guinea pig 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Cardiology Ventricular myocytes Na ca2 exchange Carvedilol 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacology. 99:40-47 |
| ISSN: | 1423-0313 0031-7012 |
| DOI: | 10.1159/000450753 |
| Popis: | Background and Aims: Carvedilol ((+/-)-1-(carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol), a β-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 β-blockers, on Na+/Ca2+ exchange current (INCX) in guinea-pig 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 µmol/l, respectively. Carvedilol at 100 μmol/l inhibited INCX in CCL39 cells expressing wild type NCX1 similar to mutant NCX1 without the intracellular regulatory loop. Carvedilol at 30 µmol/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. |
| Databáze: | OpenAIRE |
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