萘哌地尔衍生物BWYJ扩张血管效应及其机理研究

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

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 7.6 1。本品 10 -6、10 -5mol·L-1对 5 HT量效曲线也有同样的效应 ,pA2值为 6 .5 6。而当剂量为 3× 10 -6、10 -5mol·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 -5mol·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 -5mol·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。

AIM: To investigate the effects of BWYJ (naftopidil’s ramif ic ation) on the vascular activities in rabbits and to explore its vasodilative mec hanisms. METHODS: The isotonic contractions of the thoracic aort a 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 Ca 2+ free-Ca 2+ addition was designed to indirectly observe the effects of BWYJ on intracellular free Ca 2+ ([Ca 2+] i). RESULTS: BWYJ shifted the concentratio n-response curves of NA and 5-HT to right in parallel, the maximum responses w ere unchanged, and the pA 2 values were 7.61 and 6.56, respectively. Bu t it did not affect the concentration-response curve of high potassium. In Ca 2+-free medium, BWYJ 10 -7,3×10 -7, 10 -6 and 10 -5 mol·L -1 concentration-dependently inhibited the transient contracti on induced by NA and the long-lasting contraction induced by addition of Ca 2+. But BWYJ 10 -5 mol·L -1 did not inhibit the contraction ind uced by caffeine. CONCLUSION: BWYJ may be an α-adrenergic rece ptor blocker and a 5-HT receptor blocker simultaneously. The vasodilative mech anism of BWYJ may be related to its inhibiting effects on the Ca 2+-influx and Ca 2+-release mediated by α-adrenergic and 5-HT receptors.