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鞣酸可激活在人胚肾293细胞(HEK293细胞)中表达的Kv7.4以及Kv7.3/7.5钾离子通道,并降低大鼠肠系膜动脉的张力。

Tannic acid activates the Kv7.4 and Kv7.3/7.5 K(+) channels expressed in HEK293 cells and reduces tension in the rat mesenteric arteries.

作者信息

Zhang Yuanyuan, Chu Xi, Liu Ling, Zhang Nan, Guo Hui, Yang Fan, Liu Zhenyi, Dong Yongsheng, Bao Yifan, Zhang Xuan, Zhang Jianping

机构信息

Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.

Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

J Pharm Pharmacol. 2016 Apr;68(4):494-502. doi: 10.1111/jphp.12527. Epub 2016 Mar 9.

Abstract

OBJECTIVES

This study investigated the effect of tannic acid (TA), a plant-derived hydrolyzable polyphenol, on Kv7.4 and Kv7.5 K(+) channels and rat mesenteric artery.

METHODS

Whole-cell patch clamp experiments were used to record the Kv7.4 and Kv7.3/7.5 K(+) currents expressed in HEK293 cells; and the tension changes of mesenteric arteries isolated from rats were recorded using small vessel myography apparatus.

KEY FINDINGS

Tannic acid increases the Kv7.4 and Kv7.3/7.5 K(+) currents in a concentration-dependent manner (median effective concentration (EC50 ) = 27.3 ± 3.6 μm and EC50 = 23.1 ± 3.9 μm, respectively). In addition, 30 μm TA shifts the G-V curve of Kv7.4 and Kv7.3/7.5 K(+) currents to the left by 14.18 and 25.24 mV, respectively, and prolongs the deactivation time constants by 184.44 and 154.77 ms, respectively. Moreover, TA relaxes the vascular tension of rat mesenteric arteries in a concentration-dependent manner (half inhibitory concentration (IC50 ) = 148.7 ± 13.4 μm).

CONCLUSION

These results confirms the vasodilatory effects of TA on rat mesenteric artery and the activating effects on the Kv7.4 and Kv7.3/7.5 K(+) channels, which may be a mechanism to explain the vasodilatory effect and this mechanism can be used in the research of antihypertension.

摘要

目的

本研究调查了植物来源的可水解多酚单宁酸(TA)对Kv7.4和Kv7.5钾通道以及大鼠肠系膜动脉的影响。

方法

采用全细胞膜片钳实验记录HEK293细胞中表达的Kv7.4和Kv7.3/7.5钾电流;使用小血管肌动描记仪记录从大鼠分离的肠系膜动脉的张力变化。

主要发现

单宁酸以浓度依赖性方式增加Kv7.4和Kv7.3/7.5钾电流(半数有效浓度(EC50)分别为27.3±3.6μm和EC50 = 23.1±3.9μm)。此外,30μm TA使Kv7.4和Kv7.3/7.5钾电流的G-V曲线分别向左移动14.18和25.24 mV,并分别将失活时间常数延长184.44和154.77 ms。此外,TA以浓度依赖性方式松弛大鼠肠系膜动脉的血管张力(半数抑制浓度(IC50)= 148.7±13.4μm)。

结论

这些结果证实了TA对大鼠肠系膜动脉的舒张作用以及对Kv7.4和Kv7.3/7.5钾通道的激活作用,这可能是解释舒张作用的一种机制,并且该机制可用于抗高血压研究。

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