【摘要】 目的 :探讨 2 ,6 -二甲基 - 4- (3-硝基苯基 ) - 1,4-二氢 - 3,5 -吡啶二羧酸 - 3-甲酯 - 5 -正戊酯 (MN92 0 2 )的降压作用及其机制。方法 :应用清醒大鼠及肾性高血压大鼠 ,观察 MN92 0 2的降压作用 ,并采用离体兔胸主动脉张力实验观察 MN92 0 2的扩血管作用。结果 :腹腔注射 MN92 0 2 10 ,30 ,10 0 μg/ kg对正常动物和肾性高血压大鼠均可产生明显的降压作用 ,具有明显的剂量依赖关系。MN92 0 2和 Nitrendipine对抗 KCl引起家兔主动脉收缩的 IC50 分别为2 .1μmol/ L 和 3.1μmol/ L,Emax则为 6 8.8%和 5 4.9%;对抗 NE引起收缩的 IC50 分别是 2 .0 μm ol/ L 和 2 .2 μmol/L ,Emax是 34 .6 %和 32 .2 %;其作用不受内皮的影响 ;MN 92 0 2可显著抑制 NE的依赖细胞外 Ca2 +收缩反应 ,而对内 Ca2 +收缩反应则无明显抑制作用。结论 :MN92 0 2具有明显的扩血管效应 ,其作用与其抑制电压依赖性钙通道 ,减少 Ca2 +内流有关。更多还原

【Abstract】 AIM: To study the vasodilative and hypotensive effects of methyl pentyl 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-3,5-pyridinedicarboxylate( MN9202), a novel dihydropyidine calcium channel blocker. METHODS: Conscious rats and the rats with renal arterial occlusion hypertension were used to observe the reducing blood pressure activity. Rabbit aorta with endothelium or without endothelium were used to study the dilatory actions of the drug. RESULTS: MN9202 at dose of 10,30 and 100 μg/kg had obvious hypotensive effects on conscious rats and the rats with renal arterial occlusion hypertension, at dose-response manners. Both MN9202 and Nitrendipine could inhibit the rabbit aorta contraction-induced by high-K + depolarization, and their IC 50 was 2.1 μmol/L and 3.1 μmol/L, E max was 68.8% and 54.9% respectively. They could also inhibit the contraction-induced by NE,their IC 50 was 2.0 μmol/L and 2.2 μmol/L, and E max was 34.6% and 32.2% respectively. MN9202 obviously inhibited the extracellular Ca 2+-dependent component of NE-induced contraction,but had no effects on intracellular Ca 2+-dependent component. CONCLUSION: MN9202 has significant vasodilator effects and can decrease blood pressure. Its mechanisms mainly inhibit transmembrane inflow of extracellular Ca 2+ through voltage dependent calcium channel.更多还原