萘哌地尔衍生物BWYJ 扩张血管效应及其机理研究

目的: 观察萘哌地尔衍生物BWYJ 对家兔血管活动的影响, 并探讨其血管活性机理, 为该药的开发研究提供基础资料。方法: 采用家兔主动脉收缩的方法, 观察BWYJ 对去甲肾上腺素(NA)、5-羟色胺(5-HT) 和高钾量效曲线的影响;应用无Ca²⁺-复Ca²⁺的实验法, 以NA 和咖啡因为血管收缩剂, 间接观察BWYJ 对细胞内游离钙浓度(Ca²⁺]_i) 的影响,并分析其可能作用机理。结果: BWYJ 10^-7、3×10^-7、10^-6mol·L^-1使NA 量效曲线明显平行右移, 而最大反应不变, pA2 值为7.61 。本品10^-6、10^-5 mol·L^-1对5-HT 量效曲线也有同样的效应, pA2值为6.56 。而当剂量为3×10^-6、10^-5 mol·L^-1时,对氯化钾(KCl) 量效曲线没有明显影响。在无钙Krebs 液中, BWYJ 10^-7、3× 10^-7、10^-6 和10^-5 mol·L^-1呈浓度依赖性抑制NA 所致血管条的短暂收缩, 对复Ca²⁺后NA 所诱发的持续收缩也呈剂量依赖性抑制作用, 但其剂量达10^-5 mol·L^-1时尚不能抑制咖啡因在无Ca²⁺液中所致收缩。结论: BWYJ 可能是一种α受体阻断剂, 兼有拮抗5-HT 受体的作用。其扩血管的机理可能是通过阻断细胞膜上的α受体或5-HT 受体, 从而抑制这些受体中介的Ca²⁺内流和Ca²⁺释放所致。

Effects of naftopidil's ramification-BWYJ on vascular activities and it's vasodilative mechanism

AIM: To investigate the effects of BWYJ (naftopidil's ramification) on the vascular activities in rabbits and to explore its vasodilative mechanisms. METHODS: The isotonic contractions of the thoracic aorta strips in rabbits were recorded, and the effects of BWYJ on the concentration-response curves of noradrenaline (NA), high potassium and 5-hydroxytryptamine (5-HT) was observed.The procedure of Ca²⁺ free-Ca²⁺ addition was designed to indirectly observe the effects of BWYJ on intracellular free Ca²⁺ (Ca²⁺]_i).RESULTS: BWYJ shifted the concentration-response curves of NA and 5-HT to right in parallel, the maximum responses were unchanged, and the pA2 values were 7.61 and 6.56, respectively.But it did not affect the concentration-response curve of high potassium.In Ca²⁺-free medium, BWYJ 10^-7, 3×10^-7, 10^-6 and 10^-5mol·L^-1concentration-dependently inhibited the transient contraction induced by NA and the long-lasting contraction induced by addition of Ca²⁺.But BWYJ 10^-5mol·L^-1did not inhibit the contraction induced by caffeine.CONCLUSION: BWYJ may be an α-adrenergic receptor blocker and a 5-HT receptor blocker simultaneously.The vasodilative mechanism of BWYJ may be related to its inhibiting effects on the Ca²⁺-influx and Ca²⁺-release mediated by α-adrenergic and 5-HT receptors.