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电压激活的钾通道的阻断剂抑制山莨菪碱松弛去甲肾上腺素预收缩的兔主动脉平滑肌

刘书勤, 臧伟进, 李增利, 孙强, 于晓江, 罗宏丽, 朱树明

西安交通大学医学院药理学教研室.陕西，西安 710061

摘要

研究显示，山莨菪碱预处理不改变高钾引起的兔主动脉环收缩，但可明显减弱去甲肾上腺素（NA）、组织胺或5-羟色胺引起的收缩，且其减弱作用不受去除血管内皮影响。该实验观察了几种钾通道阻断剂对山莨菪碱松弛NA预收缩的兔主动脉环的影响。结果表明，1、3、10#mu#mol/L 山莨菪碱作用8 min，可使0.01#mu#mol/L NA预收缩的兔主动脉环松弛（P<0.01）。10 mmol/L CsCl、1 mmol/L 4-氨基吡啶、10#mu#mol/L BaCl_(2)、10#mu#mol/L格列本脲、3#mu#mol/L charybdotoxin和3#mu#mol/L蜂毒明肽分别与0.01#mu#mol/L NA同时加入，可增强后者收缩兔主动脉环的作用（P<0.01）。10、30 mmol/L CsCl或10、30 mmol/L 4-氨基吡啶存在时，10#mu#mol/L 山莨菪碱对NA预收缩的兔主动脉环的松弛作用减弱，松弛率与对照组比较分别有显著统计学意义（P<0.01）；10、30#mu#mol/L BaCl_(2)，10、30#mu#mol/L格列本脲，3#mu#mol/L charybdotoxin或3#mu#mol/L蜂毒明肽存在时，山莨菪碱对NA预收缩的兔主动脉环的松弛作用不受影响（P>0.05）。该研究表明，电压激活的钾通道的阻断剂抑制山莨菪碱松弛NA预收缩的兔主动脉平滑肌，初步提示血管平滑肌细胞膜上电压激活的钾通道参与山莨菪碱扩血管作用。

关键词： 钾通道; 电压激活的钾通道; 山莨菪碱; 家兔; 主动脉; 去甲肾上腺素

Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline

Liu Shuqin, Zang Weijin, Li Zengli, Sun Qiang, Yu Xiaojiang, Luo Hongli, Zhu Shuming

Department of Pharmacology, School of Medicine, Xi'an Jiaotong University.Xi'an 710061,Shaanxi

Abstract

Anisodamine, which originally extracted from scopolia tangutica and currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K+-evoked contractions in rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA), histamine or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K+-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilator action of some potassium channels activators may be inhibited or abolished in high K+ solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channels blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic ring. In a 8-minute period, anisodamine, 1, 3 and 10 #mu#mol/L, significantly relaxed the 0.01 #mu#mol/L NA precontracted aortic ring (by 19.1 ± 3.1 %, 30.1 ± 3.8 % and 38.3 ± 4.2 %, respectively) compared with the controls (by 4.8 ± 2.4 %, 5.1 ± 1.8 % and 5.6 ± 2.5 %, respectively) (P<0.01). 10 mmol/L CsCl (a non-selective potassium channel blocker), 1 mmol/L 4-aminopyridine (a selective voltage-activated potassium channel (KV) blocker), 10 #mu#mol/L BaCl_(2) (a selective inwardly-rectifying potassium channel blocker), 10 #mu#mol/L glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 #mu#mol/L charybdotoxin (a large- and intermediate- conductance Ca2+-activated potassium channels blocker) and 3 #mu#mol/L apamin (a selective small conductance Ca2+-activated potassium channel blocker) significantly increased the NA–induced contraction by 14.4 ± 3.2 %, 16.3 ± 5.8 %, 12.7 ± 4.2 %, 13.6 ± 2.0 %, 11.1 ± 5.5 % and 13.4 ± 4.3 % respectively compared with the control ( by 5.6 ± 1.2 %) (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxations of the 0.01 #mu#mol/L NA contracted rabbit aortic rings (28.8 ± 3.0 % and 15.9 ± 3.7 % or 29.7 ± 3.9 % and 19.0 ± 5.0 %) significantly deceased compared with that in the absence of any potassium channel blocker (38.3 ± 4.2 % ) (P<0.01) in a 8-minute period. However, in the presence of 10, 30 #mu#mol/L BaCl_(2), 10, 30 #mu#mol/L glibenclamide, 3 #mu#mol/L charybdotoxin, or 3 #mu#mol/L apamin, 10 #mu#mol/L anisodamine-induced relaxations (37.1 ± 3.8 %, 36.2 ± 4.7 %, 36.1 ± 2.7 %, 35.6 ± 3.3 %, 37.8 ± 2.0 % and 39.3 ± 4.7 %, respectively) did not deceased compared with the control (38.3 ± 4.2 % ) (P>0.05). This study suggests that KV blockers inhibit anisodamine-induced relaxation of the rabbit aortic smooth muscle precontracted with NA and implies that the KV in VSMC membrane plays a role in anisodamine-induced relaxation of blood vessels.

Key words: Potassium channel;Voltage-activated potassium channel;Anisodamine;Rabbit;aorta;Noradrenaline

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引用本文：

刘书勤, 臧伟进, 李增利, 孙强, 于晓江, 罗宏丽, 朱树明. 电压激活的钾通道的阻断剂抑制山莨菪碱松弛去甲肾上腺素预收缩的兔主动脉平滑肌[J]. 生理学报 2005; 57 (1): .

Liu Shuqin, Zang Weijin, Li Zengli, Sun Qiang, Yu Xiaojiang, Luo Hongli, Zhu Shuming. Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline. Acta Physiol Sin 2005; 57 (1): (in Chinese with English abstract).