张丽心,周凯.新化合物ZM对大鼠血压的影响和对肠系膜上动脉的舒张作用.[J].中南医学科学杂志.,2016,(5):510-514, 522.
新化合物ZM对大鼠血压的影响和对肠系膜上动脉的舒张作用
Effects of a New Compound ZM on Blood Pressure andMesenteric Artery in Rats
投稿时间:2016-06-08  修订日期:2016-08-28
DOI:
中文关键词:  ZM  大鼠  血压  肠系膜动脉  舒张
英文关键词:ZM  rat  blood pressure  mesenteric artery  vasodilation
基金项目:
作者单位
张丽心 西安交通大学医学院附属红会医院临床药学科,陕西 西安710054 
周凯 西安交通大学第二附属医院药剂科 
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中文摘要:
      目的 研究新合成的二氢吡啶类化合物ZM对大鼠血压的影响和对肠系膜上动脉的舒张作用及机制。方法自发性高血压大鼠(SHR)分为溶媒组6只,给药组各8只(ZM 0.2 mg/kg组,ZM 0.4 mg/kg组),采用鼠尾无创血压测量法测量给药前及ZM灌胃给药1 h后大鼠收缩压和舒张压的变化。SD大鼠32只用于体外实验,利用小血管张力测量系统研究ZM对SD大鼠完整内皮及去内皮肠系膜上动脉的扩张作用;研究ZM对KCl、CaCl2、苯肾上腺素和U46619收缩血管量效曲线的影响;研究在不含钙的缓冲液中ZM对苯肾上腺素、CaCl2及咖啡因收缩血管的影响。结果ZM灌胃给药0.2 mg/kg降低自发性高血压大鼠收缩压和舒张压分别为16%和17%;0.4 mg/kg降低收缩压和舒张压分别为24%和25%。ZM(10-9~10-4 mol/L)呈浓度依赖性地舒张大鼠肠系膜上动脉,去内皮动脉和完整内皮动脉相比较舒张作用间差异无显著性;ZM(3×10-8 mol/L,3×10-7 mol/L)使KCl、CaCl2、苯肾上腺素和U46619收缩血管量效曲线非平行右移;在不含钙的缓冲液中ZM(3×10-8 mol/L,3×10-7 mol/L,3×10-6 mol/L)可以抑制CaCl2引起的血管收缩,对苯肾上腺素及咖啡因引起的收缩血管无影响。结论ZM可以降低大鼠血压,呈浓度依赖性地扩张大鼠肠系膜上动脉,其主要作用机制可能与抑制血管平滑肌细胞钙离子内流有关。
英文摘要:
      Objective The aim of this study was to assess the effects of a new synthetic dihydropyridines compound (ZM) on rat blood pressure and vasodilation of superior mesenteric artery and its mechanism.MethodSpontaneously hypertensive rats were divided into the vehicle group,administration group(ZM 0.2 mg/kg,ZM 0.4 mg/kg).The blood pressure of rats was measured using a non-invasive tail cuff blood pressure system in vivo before administration and 1 h after gavage.32 SD(Sprague-Dawley)rats were used in vitro,Isometric tension of artery ring segments was recorded by myography system in vitro for the estimation of the effects of ZM on the vasoconstriction dose-response curves of KCl,CaCl2,phenylephrine and U46619.Effects of ZM on the contraction of artery ring segments in calcium-free Krebs solution with phenylephrine,CaCl2 and caffine added were also evaluated.ResultsZM (0.2 mg/kg) decreased the systolic and diastolic blood pressure of spontaneously hypertensive rats 1h after gavage by 16% and 17%.ZM (0.4 mg/kg) decreased by 24% and 25% respectively.There was no obvious difference of the vasorelaxation between intact and denuced endothelium mesenteric arterial ring segments in ZM(10-9~10-4 mol/L).ZM(3×10-8 mol/L,3×10-7 mol/L)shifted the concentration-contratile curves induced by KCl,CaCl2,phenylephrine and U46619 towards the right in a non-parallel manner with the decreased Emax.ZM(3×10-8 mol/L,3×10-7 mol/L,3×10-6 mol/L)obviously inhibited the contraction induced by CaCl2,but did not inhibit the contraction induced by phenylephrine and caffine in calcium-free Krebs solution.ConclusionZM can lower blood pressure of rats in vivo and concentration-dependently relax the mesenteric artery in vitro.The mechanism of the effects of ZM was mainly through inhibiting extracellar calcium of artery muscle.
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