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作 者:刘宜先[1] 董京辉[1] 高璐[1] 马慧娟[1] 武宇明[1] 张翼[1] 何瑞荣[1]
机构地区:[1]河北医科大学基础医学院生理学教研室,河北石家庄050017
出 处:《中国药理学与毒理学杂志》2009年第3期161-167,共7页Chinese Journal of Pharmacology and Toxicology
基 金:The project supported by Foundation ofScience &Technology Bureau of Hebei Province(062761773);Natural Science Foundation of Education Bureau of Hebei Province(Z2006110)~~
摘 要: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 Rhy10, 50和100μmo·lL-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 10μmol.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100μmol·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 1mmol·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。AIM To elucidate the effect of rhyncho- phylline(Rhy) on carotid sinus baroreceptor activity (CBA). METHODS By recording sinus nerve affer- ent discharge activity with isolated carotid sinus perfu- sion, parameters of CBA, such as peak slope (PS), peak integral value ( PIV ), threshold pressure (TP) and saturation pressure (SP) were examined. (1)Rhy 10, 50, and 100μmol· L-1, dissolved in K-H solu- tion, 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. (2) NG-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 per- fused into isolated carotid sinus, and effects of them on the response of carotid baroreceptor to Rhy were ob- served. RESULTS (1) By perfusing the isolated ca- rotid sinus with Rhy 10 μmol· L-1, PS decreased from (19.2 ±0.3)% to (18.2±0. 1)%·kPa-land the PIVdecreased 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. (2)Pretreatment with L-NAME 100 μmol·L-1 did not affect inhibitory action of Rhy 50 μmol·L-1 on CBA. (2)Pretreatment with TEA 1 mmol· L-1 had no effect on inhibitory effect of Rhy 50 μmol·L-1 on CBA. (4)Pretreatment 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.
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