中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
3期
161-167
,共7页
刘宜先%董京辉%高璐%马慧娟%武宇明%张翼%何瑞荣
劉宜先%董京輝%高璐%馬慧娟%武宇明%張翼%何瑞榮
류의선%동경휘%고로%마혜연%무우명%장익%하서영
钩藤碱%颈动脉窦%压力感受器%Bay%K8644
鉤籐堿%頸動脈竇%壓力感受器%Bay%K8644
구등감%경동맥두%압력감수기%Bay%K8644
rhynchophylline%carotid sinus baroreceptor%Bay K8644
目的 探讨钩藤碱(Rhy)对大鼠颈动脉窦压力感受器活动的影响及其有关机制.方法 通过隔离灌流颈动脉窦区的方法来获得颈动脉窦压力感受器活动的各项参数,阈压(TP)、饱和压(SP)、最大斜率(PS)和窦神经放电的最大积分值(PIV).① Rhy 10, 50和100 μmol·L-1用K-H液稀释后,隔离灌流颈动脉窦区.待钩藤碱发挥作用后,用K-H液冲洗恢复,在给药前后以阶梯方式升降窦内压以刺激颈动脉窦压力感受器,同时记录窦神经传入放电及积分.②分别预先灌流一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(L-NAME)、K+通道阻断剂四乙胺(TEA)和L-钙通道开放剂Bay K8644,观察他们对钩藤碱效应的影响.结果 ①Rhy 10 μmol·L-1灌流隔离的颈动脉窦区,PS从(19.2±0.3)%降至(18.2±0.1)%·kPa-1,PIV从(219.3±3.3)%降至(199.1±3.8)%,同时TP和SP分别从(8.2±0.3)和(21.5±0.1)增加至(9.1±0.1)kPa和(22.1±0.1)kPa.用Rhy 50和100 μmol·L-1进行灌流时,如PS,TP和SP的变化均呈浓度依赖性,表明Rhy可以抑制CBA.②预先灌流L-NAME不能阻断Rhy 的效应.③预先灌流K+通道阻断剂TEA 1 mmol·L-1也不能阻断Rhy对颈动脉窦压力感受器放电活动的抑制.④预先灌流L-钙通道开放剂Bay K8644可大部分阻断Rhy的作用.结论 Rhy可直接抑制大鼠颈动脉窦压力感受器传入神经放电活动,其机制可能为Rhy抑制了动脉压力感受器上的Ca2+内流.
目的 探討鉤籐堿(Rhy)對大鼠頸動脈竇壓力感受器活動的影響及其有關機製.方法 通過隔離灌流頸動脈竇區的方法來穫得頸動脈竇壓力感受器活動的各項參數,閾壓(TP)、飽和壓(SP)、最大斜率(PS)和竇神經放電的最大積分值(PIV).① Rhy 10, 50和100 μmol·L-1用K-H液稀釋後,隔離灌流頸動脈竇區.待鉤籐堿髮揮作用後,用K-H液遲洗恢複,在給藥前後以階梯方式升降竇內壓以刺激頸動脈竇壓力感受器,同時記錄竇神經傳入放電及積分.②分彆預先灌流一氧化氮閤酶抑製劑左鏇硝基精氨痠甲酯(L-NAME)、K+通道阻斷劑四乙胺(TEA)和L-鈣通道開放劑Bay K8644,觀察他們對鉤籐堿效應的影響.結果 ①Rhy 10 μmol·L-1灌流隔離的頸動脈竇區,PS從(19.2±0.3)%降至(18.2±0.1)%·kPa-1,PIV從(219.3±3.3)%降至(199.1±3.8)%,同時TP和SP分彆從(8.2±0.3)和(21.5±0.1)增加至(9.1±0.1)kPa和(22.1±0.1)kPa.用Rhy 50和100 μmol·L-1進行灌流時,如PS,TP和SP的變化均呈濃度依賴性,錶明Rhy可以抑製CBA.②預先灌流L-NAME不能阻斷Rhy 的效應.③預先灌流K+通道阻斷劑TEA 1 mmol·L-1也不能阻斷Rhy對頸動脈竇壓力感受器放電活動的抑製.④預先灌流L-鈣通道開放劑Bay K8644可大部分阻斷Rhy的作用.結論 Rhy可直接抑製大鼠頸動脈竇壓力感受器傳入神經放電活動,其機製可能為Rhy抑製瞭動脈壓力感受器上的Ca2+內流.
목적 탐토구등감(Rhy)대대서경동맥두압력감수기활동적영향급기유관궤제.방법 통과격리관류경동맥두구적방법래획득경동맥두압력감수기활동적각항삼수,역압(TP)、포화압(SP)、최대사솔(PS)화두신경방전적최대적분치(PIV).① Rhy 10, 50화100 μmol·L-1용K-H액희석후,격리관류경동맥두구.대구등감발휘작용후,용K-H액충세회복,재급약전후이계제방식승강두내압이자격경동맥두압력감수기,동시기록두신경전입방전급적분.②분별예선관류일양화담합매억제제좌선초기정안산갑지(L-NAME)、K+통도조단제사을알(TEA)화L-개통도개방제Bay K8644,관찰타문대구등감효응적영향.결과 ①Rhy 10 μmol·L-1관류격리적경동맥두구,PS종(19.2±0.3)%강지(18.2±0.1)%·kPa-1,PIV종(219.3±3.3)%강지(199.1±3.8)%,동시TP화SP분별종(8.2±0.3)화(21.5±0.1)증가지(9.1±0.1)kPa화(22.1±0.1)kPa.용Rhy 50화100 μmol·L-1진행관류시,여PS,TP화SP적변화균정농도의뢰성,표명Rhy가이억제CBA.②예선관류L-NAME불능조단Rhy 적효응.③예선관류K+통도조단제TEA 1 mmol·L-1야불능조단Rhy대경동맥두압력감수기방전활동적억제.④예선관류L-개통도개방제Bay K8644가대부분조단Rhy적작용.결론 Rhy가직접억제대서경동맥두압력감수기전입신경방전활동,기궤제가능위Rhy억제료동맥압력감수기상적Ca2+내류.
AIM To elucidate the effect of rhynchophylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve afferent discharge activity with isolated carotid sinus perfusion, parameters of CBA, such as peak slope (PS), peak integral value (PIV), threshold pressure (TP) and saturation pressure (SP) were examined. ①Rhy 10, 50, and 100 μmol·L-1, dissolved in K-H solution, was perfused into isolated carotid sinus, then the effects of Rhy on parameters of CBA were observed while intrasinus pressure was altered in a stepwise manner. ②NG-nitro-L-arginine methyl ester (L-NAME) 10 mmol·L-1, tetraethylammonium (TEA) 1 mmol·L-1 and Bay K8644 500 nmol·L-1 were perfused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were observed. RESULTS ① By perfusing the isolated carotid sinus with Rhy 10 μmol·L-1, PS decreased from (19.2±0.3)% to (18.2±0.1)%·kPa-1and the PIV decreased from (219.3±3.3)% to (199.1±3.8)%, while TP and SP increased from (8.2±0.3) to (9.1±0.1)kPa and (21.5±0.1) to (22.1±0.1)kPa, respectively. By perfusing with Rhy 50 and 100 μmol·L-1, the changes in PS, TP and SP were in concentration-dependent manner, and this indicated inhibitory effect of Rhy on CBA. ②Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. ③Pretreatment with TEA 1 mmol·L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. ④Pretreatment with Bay K8644 500 nmol·L-1 could mostly attenuate effect of Rhy 50 μmol·L-1 on CBA. CONCLUSION Rhy inhibits CBA via blocking calcium influx in baroreceptor nerve ending.