Effects of labedipinedilol-A, third-generation dihydropyridine-type calcium blocker, on ouabain-induced arrhythmia
✍ Scribed by Jhy-Chong Liang; An-Hsiang Huang; Jiunn-Ren Wu; Shu-Fen Liou; Zen-Kong Dai; Ing-Jun Chen; Jwu-Lai Yeh
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 175 KB
- Volume
- 69
- Category
- Article
- ISSN
- 0272-4391
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✦ Synopsis
Labedipinedilol-A, a novel dihydropyridine-type calcium antagonist with a/b-adrenoceptor blocking properties, has been reported to produce a cardioprotective effect against ischemia reperfusion injury in rats. We investigated the protective effects of labedipinedilol-A on ouabain-induced tonotropy and arrhythmias in isolated whole atria, and using patch-clamp techniques to study the underlying mechanism of its antiarrhythmic activity on isolated cardiac myocytes. Labedipinedilol-A (10 mM) suppressed the tonotropic effect of ouabain significantly and prolonged the onset time of extrasystole (arrhythmia) induced by ouabain in isolate atria. In the voltage-clamp study, labedipinedilol-A (1-100 mM) reduced the peak amplitude of sodium inward current (I Na ) and L-type calcium current (I Ca-L ), and shifted the current-voltage (I-V) curve upward in a concentration-dependent manner. In contrast, the addition of labedipinedilol-A increased transient outward potassium current (I to ) and inward rectifier potassium current (I K1 ) significantly. Labedipinedilol-A (10 mM) also effectively depressed the isoproterenol-induced increase in the Ca 21 current. These results show that labedipinedilol-A blocks I Ca-L and I Na , and increases I to and I K1 . These findings indicate that labedipinedilol-A produces direct cardiac action, probably due to the inhibition of cardiac Na 1 and Ca 21 channels. Our results suggest that labedipinedilol-A may reduce the membrane conduction through inhibition of ionic channels which decrease ouabaininduced arrhythmia.