EMD_(56431)对豚鼠气管平滑肌的作用

目的　观测新型的ＡＴＰ敏感钾通道开放剂ＥＭＤ５６４３１（ＥＭＤ） 的平喘作用，并与钙通道阻滞剂粉防己碱（ｔｅｔｒａｎ ｄｒｉｎｅ，Ｔｅｔ）比较。方法　豚鼠离体气管法和整体药物引喘法。结果　ＥＭＤ 能抑制ＫＣｌ 所致豚鼠气管螺旋条的收缩反应，其抑制作用随［Ｋ＋］ｏ 浓度的增高而减弱；ＥＭＤ 能浓度依赖性地使氨甲酰胆碱和组胺的量效曲线右移，最大效应降低，均表现为非竞争性拮抗，ｐＤ′２ 值分别为４－４５ 和４－４０ ；组胺喷雾引起的豚鼠哮喘模型中，ＥＭＤ 灌胃能剂量依赖性地使豚鼠的引喘潜伏期延长，抽搐动物数亦随剂量增加而减少（ｎ ＝ ８ ，Ｐ＜ ０－０５）。结论　ＥＭＤ 的支气管扩张作用在于开放钾通道，其作用强于Ｔｅｔ，两者具有协同作用。ＥＭＤ 单用或与Ｔｅｔ 小剂量合用显示出较好的效果

Effects of EMD_(56431) on guinea pig airway smooth muscle

AIM To elucidate the effects of EMD 56431 (EMD) on guinea pig airway smooth muscle and compare with tetrandrine (Tet). METHODS The methods of isolated guinea pig trachea and the whole animals asthma in conscious guinea pigs were used to observe antiasthmatic effect. RESULTS EMD inhibited KCl induced contraction in guinea pig isolated tracheal spirals. Its effect decreased whileK+]Oconcentrationsincreased.EMDcouldmarked lyinhibitthecontractionoftrachealspiralsinducedbycarbacholandhistaminerespectivelyinaconcentra tion dependentmanner,shiftedthecumulativedose responsecurvesofcarbacholandhistaminetoright,andreducedthemaximalefficacyofcontractioninanoncompetitiveantagonisticmanner.ThepD′2val uesofcarbacholandhistaminewere4-45and4-40respectively.EMDinadose dependentmannerpro longedthetimebeforeconsciousguineapigcollapsedinresponsetohistamineaerosolandreducedthenum berofanimalscollapsedduring6min(n=8,P<0-05).CONCLUSIONSEMDinhibitsairwaysmoothmusclecontractionthroughitspotassiumchannelopeningeffectandhasgreatereffectsthanTetasabronchodilatorintheguineapig.TheressynergismbetweenEMDandTet.