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 and Mesenteric Artery in Rats

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、Ca Cl2、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、Ca Cl2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^-4mol/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^-8mol/L,3×10-7mol/L）使KCl、Ca Cl2、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^-8mol/L,3×10-7mol/L,3×10-6mol/L）可以抑制Ca Cl2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。

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. Method Spontaneously 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,Ca Cl2,phenylephrine and U46619.Effects of ZM on the contraction of artery ring segments in calcium-free Krebs solution with phenylephrine,Ca Cl2 and caffine added were also evaluated. Results ZM（ 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^-4mol/L）.ZM（ 3×10^-8mol/L,3×10-7mol/L） shifted the concentration-contratile curves induced by KCl,Ca Cl2,phenylephrine and U46619 towards the right in a non-parallel manner with the decreased Emax.ZM（ 3×10^-8mol/L,3×10-7mol/L,3×10-6mol/L） obviously inhibited the contraction induced by Ca Cl2,but did not inhibit the contraction induced by phenylephrine and caffine in calcium-free Krebs solution. Conclusion ZM 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.