盐酸埃他卡林对自发性高血压大鼠尾动脉血管条的舒张作用  

Vasodilating action induced by iptakalim hydrochloride in tail artery strips of spontaneously hypertensive rats

作　　者：贾国栋[1] 刘国树[1] 汪海[2] 

机构地区：[1]解放军总医院南楼保健科,北京市100853 [2]解放军军事医学科学院毒物药物研究所,北京市100850

出　　处：《中国组织工程研究与临床康复》2007年第2期234-237,241,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：国家"八六三"计划重大专项课题资助(2002AA2Z3137)~~

摘　　要：目的:分析新型抗高血压药物盐酸埃他卡林对自发性高血压大鼠和正常血压Wistar-Kyoto大鼠阻力小动脉的舒张作用特点。方法:实验于2004-03/2005-01在解放军军事医学科学院毒物药物研究所完成。①选取12周龄雄性自发性高血压大鼠30只作为自发性高血压组,以12周龄雄性Wistar-Kyoto大鼠35只作为正常对照组。盐酸埃他卡林纯度大于99.5%(由解放军军事医学科学院毒物药物研究所合成);乙酰胆碱,L-NAME,吲哚美辛,格列苯脲,4-氨基吡啶,四乙铵均购自美国Sigma化学公司。②尾动脉血管条的制备:两组大鼠处死后迅速分离尾动脉,每只鼠制备2～4个螺旋状血管条,其中1～2个血管条去除内皮,其余血管条保持内皮完整。将血管条的两端扎紧,悬挂于含5mL Krebs-Ringer营养液的37℃恒温浴槽内,下端固定,上端通过张力换能器连于自动平衡记录仪,记录血管条的张力变化,并持续通入体积分数为0.95的O2和0.05的CO2混和气。制备完毕的血管条用于以下各独立实验。③乙酰胆碱诱发大鼠尾动脉内皮依赖性舒张反应实验:自发性高血压组取14个去内皮血管条,14个内皮完整血管条;正常对照组取12个去内皮血管条,12个内皮完整血管条。用40 mmol/L的KCl对两组大鼠尾动脉去内皮及内皮完整血管条进行预收缩,当血管条收缩达到稳定后,累积性加入10-8～10-4 mol/L乙酰胆碱。以KCl诱发最大稳定收缩幅度为100%,检测血管舒张率。④盐酸埃他卡林诱发大鼠尾动脉舒张反应实验:自发性高血压组取12个去内皮血管条,14个内皮完整血管条;正常对照组取10个去内皮血管条,取12个内皮完整血管条。预收缩过程同上,当血管条收缩达到稳定后,累积性加入10-7～10-3 mol/L盐酸埃他卡林,检测血管舒张率。⑤钾通道阻断剂影响盐酸埃他卡林舒血管作用的实验:自发性高血压组、正常对照组各取12个内皮完整血管条。首先将血管条AIM： To study the vasodilating action induced by the novel antihypertensive drug iptakalim hydrochloride （Ipt） in tail artery of spontaneously hypertensive rats （SHR） and normotansive Wistar-Kyoto rats （WKY）. METHODS： This experiment was carded out in the Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences between March 2004 and January 2005. ① A total of 30 twelve-week-old male SHR and 35 age-matched male normotensive WKR were adopted and allocated into SHR group and WKY （control） group. The following drugs ware used： Ipt which purity was more than 99.5% （synthetized by Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences）; acetylchollne, L-NAME, indomethacin, gllbenclamide, 4-aminopyddine and tetraethylammonium were obtained from Sigma Chemicals, Co.②Rat tail artery helical strips preparation： SHR and WKY were killed, Then each tail artery was rapidly isolated and cut helically, 2-4 strips in each rat. The endothelium of 1-2 strips was removed while other artery strips were retained completely. All strips were pricked in both ends and mounted between two stainless-steel stirrups in organ chambers filled with 5 mL modified Krebs-Ringer bicarbonate buffer at 37 ℃ with the gas containing 95% O2 and 5% CO2. One of the rat tall artery helical strips was anchored in the organ chamber and the other was connected to a strain gauge for the measurement of isometric tension. And then, the strips were used in following experiments.③Acetylcholine-induced endothellum-dependent relaxation was observed in rat tail artery strips precontracted with potassium chloride at the concentration of 40 mmol/L in both 14 SHR and 12 WKY with or without strips, respectively, The vascular relaxation induced by acetylcholine at the cumulative doses （from 10^-3 to 10^-4 mol/L）during the sustained phase of tension generated by the vasoconstrictor, and vasodilating rate was examined when.the maximum contraction amplitude was defined as 100%.④The vaso

关 键 词：抗高血压药 尾 动脉 钾通道 

分 类 号：R544.1[医药卫生—心血管疾病]