Cibenzoline Has an Inhibitory Effect on Vasorelaxation Mediated by Adenosine Triphosphate-Sensitive K+ Channels in the Rat Carotid Artery
Cibenzoline Has an Inhibitory Effect on Vasorelaxation Mediated by Adenosine Triphosphate-Sensitive K+ Channels in the Rat Carotid Artery
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西苯唑啉对大鼠颈动脉中三磷酸腺苷敏感 K 通道介导的血管舒张有抑制作用
DOI：
10.1213/00000539-200108000-00008
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Y. Hatano
中科院分区：
文献类型：
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作者：
H. Kinoshita;H. Iranami;Y. Kimoto;M. Dojo;Y. Hatano
心肌细胞研究表明，西苯唑啉可降低三磷酸腺苷 (ATP) 敏感的 K+ 电流，表明这种 Ia 类抗心律失常药物可能会改变这些制剂中 ATP 敏感的 K+ 通道的活性。尚未研究Ia类抗心律失常药物对离子通道介导的血管舒张的影响。因此，我们设计本研究是为了检验西苯唑啉是否可能在离体大鼠颈动脉中对选择性 ATP 敏感 K+ 通道开放剂 levcromakalim 产生反应而产生血管舒张变化。没有内皮的大鼠颈动脉环被悬挂以进行等长力记录。以累积方式获得浓度响应曲线。在去氧肾上腺素 (3 × 10−7 M) 的次最大收缩期间，获得了对 levcromakalim (10−8 至 10−5 M) 或 1-羟基-2-氧代-3-(N-甲基-3-氨基丙基)-3-甲基-1-三氮烯 (NOC-7; 10−10 至 10−5 M) 的血管舒张作用。在去氧肾上腺素收缩期间，左旋卡林诱导浓度依赖性血管舒张。选择性 ATP 敏感 K+ 通道拮抗剂格列本脲 (5 × 10−6 M) 完全消除了 levcromakalim 引起的血管舒张作用，而选择性 Ca2+ 依赖性 K+ 通道拮抗剂伊贝里奥毒素 (5 × 10−8 M) 则不影响舒张作用。西苯唑啉（10−6 至 10−5 M）以浓度依赖性方式显着降低 levcromakalim 的血管舒张作用。相比之下，西苯唑啉 (10−5 M) 不会改变一氧化氮供体 NOC-7 的血管舒张作用。这些结果表明，从临床相关浓度来看，一种新型 Ia 类抗心律失常药物西苯唑啉会损害 ATP 敏感 K+ 通道介导的颈动脉血管舒张。
Studies in cardiac myocytes have shown that cibenzoline reduces adenosine triphosphate (ATP)-sensitive K+ currents, suggesting that this class Ia antiarrhythmic drug may modify the activity of ATP-sensitive K+ channels in these preparations. The effects of class Ia antiarrhythmic drugs on vasodilation mediated by ion channels have not been studied. Therefore, we designed this study to examine whether cibenzoline may produce changes in vasorelaxation in response to a selective ATP-sensitive K+ channel opener, levcromakalim, in the isolated rat carotid artery. Rings of rat carotid arteries without endothelium were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative fashion. During submaximal contraction to phenylephrine (3 × 10−7 M), vasorelaxation in response to levcromakalim (10−8 to 10−5 M) or 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10−10 to 10−5 M) was obtained. During contraction to phenylephrine, levcromakalim induced concentration-dependent vasorelaxation. A selective ATP-sensitive K+ channel antagonist, glibenclamide (5 × 10−6 M), completely abolished vasorelaxation in response to levcromakalim, whereas a selective Ca2+-dependent K+ channel antagonist, iberiotoxin (5 × 10−8 M), did not affect the relaxation. Cibenzoline (10−6 to 10−5 M) significantly reduced vasorelaxation to levcromakalim in a concentration-dependent fashion. In contrast, cibenzoline (10−5 M) did not alter vasorelaxation to a nitric oxide donor, NOC-7. These results suggest that from the clinically relevant concentrations, a novel class Ia antiarrhythmic drug, cibenzoline, impairs carotid vasodilation mediated by ATP-sensitive K+ channels.