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中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (2): 140-145.

• 研究原著 • 上一篇    下一篇

新型抗高血压药物盐酸埃他卡林对小动脉的选择性扩张作用及其药理学机制

贾国栋, 崔文玉1, 龙超良1, 刘国树, 汪海1   

  1. 中国人民解放军总医院南楼心肾科, 北京 100853;
    1军事医学科学院毒物药物研究所, 北京 100850
  • 收稿日期:2003-07-14 修回日期:2003-08-29 出版日期:2004-02-26 发布日期:2020-11-16
  • 通讯作者: 汪海,男, 博士, 教授, 博士生导师, 国家新药审评委员, 研究方向:心血管药理学。Tel:010-66932651 Fax:010-68211656 E-mail: wh@nic.bmi.ac.cn
  • 作者简介:贾国栋, 男, 博士, 主治医师, 主要从事心血管疾病临床和基础研究。Tel:010-66937653  E-mail:301jgd@sina.com
  • 基金资助:
    国家863 计划重大专项(NO.2002AA2Z3137)

Selective vasodilating action in small artery and its pharmacological mechanisms of novel antihypertensive drug iptakalim hydrochloride

JIA Guo-Dong, CUI Wen-Yu1, LONG Chao-Liang1, LIU Guo-Shu, WANG Hai1   

  1. Department of Cardiology and Nephrology, PLA General Hospital, Beijing 100853, China;
    1Institute of Pharmacologyand Toxicology, Academy of Military Medical Science, Beijing 100850, China
  • Received:2003-07-14 Revised:2003-08-29 Online:2004-02-26 Published:2020-11-16

摘要: 目的: 研究新型抗高血压药物盐酸埃他卡林(Ipt) 对小动脉的作用特性及其药理学机制。方法: 采用大鼠尾动脉螺旋状血管条和主动脉离体血管环两种组织, 对比观察盐酸埃他卡林对大、小动脉扩张作用的药理学特性, 并且利用膜片钳技术观察盐酸埃他卡林对大鼠尾动脉平滑肌细胞钾电流的影响。结果: Ipt 在10-7 ~ 10-3 mol·L-1 范围内对KCl 预致收缩的大鼠尾动脉血管条产生剂量依赖性舒张反应, 且具有部分内皮依赖性, 但对主动脉离体血管环无明显的舒张反应, 该作用在高血压状态时显著增强, 能被ATP 敏感性钾通道特异性阻断剂格列苯脲阻断, 并且对大鼠尾动脉平滑肌细胞的钾电流具有显著增强作用。结论: 盐酸埃他卡林具有选择性舒张小动脉作用, 具有ATP 敏感性钾通道开放剂的主要药理学特征。

关键词: 盐酸埃他卡林, ATP 敏感性钾通道开放剂, 大鼠尾动脉, 主动脉, 钾电流

Abstract: AIM: To study the selective vasodilating action in small artery and its pharmacological mechanisms of the novel antihypertensive drug iptakalim hydrochloride (Ipt).METHODS: Differences of the vasodilating action of Ipt in big artery and small artery were studied using isolated rat tail artery helical strips and aortic rings, and the effects of Ipt on potassium currents in smooth muscle cells derived from rat tail artery were observed by using patch clamp technique.RESULTS: The vasodilating action of Ipt at 10-7-10-3 mol·L-1 was observed in rat tail artery strips precontracted with potassium chloride (KCl) in a concentration-dependent manner, and the vasodilating action presented a partially endothelium-dependent character, but no significantly vasodilating effect was seen in rat aortic rings.Ipt-induced relaxation in tail artery was significantly greater in spontaneously hypertensive rat than that in normotensive rat, and the vasodilating action of Ipt in small artery could be markedly antagonized by glibenclamide (10 μmol·L-1) which only inhibited ATP-sensitive potassium channels.Moreover, the potassium currents in smooth muscle cells derived from rat tail artery could be augmented by Ipt.CONCLUTION: The novel antihypertensive drug iptakalim hydrochloride has a selective vasodilating action in small artery, and it has major pharmacological characters of ATP-sensitive potassium channel openers.

Key words: iptakalim hydrochloride, ATP-sensitive potassium channel openers, rat tail artery, rat aorta, potassium currents

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