摘要
目的观察萘哌地尔衍生物YMⅢ对家兔血管活动的影响并探讨其血管活性机制,为该药的开发研究提供基础资料。方法采用家兔胸主动脉条收缩的方法,观察YMⅢ对去甲肾上腺素(NA)、5-羟色胺(5-HT)、和高钾缩血管量效曲线的影响;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YMⅢ对细胞内游离钙浓度([Ca2+]i)的影响,并分析其可能作用的钙通道。结果YMⅢ10-8、5×10-8、10-7mol·L-1使NA量效曲线明显平行右移,而最大反应不变,pA2值为8.00;本品10-6、5×10-6mol·L-1对氯化钾(KCl)量效曲线没有明显影响,但当浓度为10-5mol·L-1时,能使高钾量效曲线呈非平行右移,最大反应压低,pD′2值为4.26;本品10-7、10-6、10-5mol·L-1虽使5-HT量效曲线的最大反应有降低趋势,但无统计学意义。在无钙Krebs液中,YMⅢ10-8、5×10-8、10-7mol·L-1呈浓度依赖性抑制NA所致血管条的短暂收缩,对复钙后NA所诱发的持续性收缩也呈浓度依赖性抑制作用,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YMⅢ可能是一种α受体阻断剂,其扩血管机制可能是阻断细胞膜上的α受体,从而抑制受体中介的Ca2+内流和Ca2+释放。
Aim To investigate the effects of YMⅢ,a derivative of naftopidil, on the vascular contractive activities in rabbit aorta and to explore its vasodilative mechanisms.Methods The isotonic contractions of the thoracic aorta strips from rabbits were recorded, and the effects of YMⅢ on the concentration-response curves of noradrenaline（NA）,high potassium and 5-hydroxytryptamine（5-HT）were observed.Intracellular free Ca^2＋（[Ca^2＋]i）was investigated in the pressence of and the absence of YMⅢ in different conditions.Results YMⅢ（10^-8,5×10^-8,10^-7 mol·L^-1）shifted the concentration-response curve of NA with a parallel manner to right, the maximum response was unchanged and the pA2 value was 8.00; YMⅢ （10^-5 mol·L^-1）also shifted the concentration-response curve induced by high potassium to right but with non-parallel manner,the response was depressed and the pD′2 value was 4.26. However, YMⅢ（10^-7,10^-6,10^-5 mol·L^-1）had no statistical influence on the concentration-response curve induced by 5-HT, although it tended to depress the response of the curve at 10^-5 mol·L^-1.In Ca^2＋-free medium,YMⅢ （10^-8,5×10^-8 and 10^-7mol·L^-1） significantly inhibited the transient contraction induced by NA and the long-lasting one induced by addition of Ca^2＋ with a concentration-dependent manner.But even at 10^-5 mol·L^-1,it did not inhibit the contraction induced by caffeine.Conclusions YMⅢ may be α-adrenergic receptor blocker.Its vasodilative mechanism may be related to：blocking α-adrenergic receptor on cell membrane resulting in the inhibition on the influx of extracellular Ca^2＋ and the release of intracellular calcium.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第11期1522-1526,共5页
Chinese Pharmacological Bulletin
