ATP敏感性钾通道SUR2B/Kir6.1亚型选择性开放剂纳他卡林的心血管药理学作用特征  

The cardiovascular actions of natakalim,a highly selective opener of SUR2B/Kir6.1 subtype of ATP-sensitive potassuim channels

作　　者：唐渊[1] 王汝欢[2] 潘志远[1] 崔文玉[1] 汪海[1,2,3] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]北京赛德维康医药研究院,北京100039 [3]军事医学科学院卫生学环境医学研究所,天津300050

出　　处：《中国药理学通报》2009年第2期164-168,共5页Chinese Pharmacological Bulletin

基　　金：国家高技术研究发展计划(863计划)重大专项资助项目(No2002AA2Z3137)

摘　　要：目的研究SUR2B/Kir6.1亚型KATP通道开放剂纳他卡林的心血管药理学作用。方法(1)血流动力学测定:戊巴比妥钠腹腔注射麻醉大鼠,从颈总动脉插管至左心室,连接八导生理记录仪记录心功能的变化。(2)制备大鼠离体工作心脏,观察纳他卡林对其心功能的影响。(3)制备大鼠尾动脉血管条,用去甲肾上腺素预收缩后,观察累积给予纳他卡林对血管张力的影响。结果纳他卡林10-8～10-4mol.L-1对大鼠离体工作心脏功能无影响;对大鼠尾动脉血管条具有内皮细胞依赖性舒张作用。麻醉大鼠,纳他卡林0.5、2、8mg.kg-1静脉注射可剂量依赖性降低血压,纳他卡林8mg.kg-1抑制心脏的收缩和舒张功能,其效应可被格列苯脲和L-NAME拮抗。结论纳他卡林对心脏无直接作用,可通过舒张血管降低血压;纳他卡林的心血管药理学作用与其选择性开放KATP通道、促进内皮细胞释放NO有关。Aim To investigate the cardiovascular pharmacological effects of natakalim, a selective KATP channel SUR2B/Kir6. 1 subtype opener natakalim. Methods （1） After adult male Wistar rats were anesthetized with pentobarbital-Na and catheterized into left ventricle via carotid artery, an eight-channel direct-writing oscillorgraph was used to evaluate effects of natakalim on heart functions. （2） The cardiac effects of natakalim were evaluated on isolated working hearts. （3） After the rat tail artery strips were pretreated with NE, the vasodilative action of natakalim was observed. Results Natakalim at concentrations ranging from 0. 01 μmol· L^-1 to 100 μmol · L^-1 had no effects on isolated working heart derived from rats; however, natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE. Natakalim 0. 5, 2 and 8 mg·kg^-1 decreased blood pressure dose-dependently in anaesthetied rats. Natakalim 8 mg· kg^-1 inhibited cardiac systolic and diastolic function, and these effects were antagonized by glibenclamide or L-NAME. Conclusion Natakalim had no directed effects on heart and decreased blood pressure via dilating vessels. The cardiovascular effects of natakalim may be due to its selective action of SUR2B/Kir6. 1 channel , and increasing release of nitric oxide.

关 键 词：纳他卡林 K_ATP通道 SUR2B/Kir6.1通道 内皮细胞 心血管作用 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]