血管活性剂对高血压患者肠系膜动脉平滑肌细胞钙激活钾通道活性的调控作用  

Regulation of calcium-activated potassium channels of mesenteric artery smooth muscle from patients with essential hypertension by endothelin-1 and prostagl E_1

作　　者：罗兴林[1] 魏宗德[1] 何川[1] 杨艳[2] 王文艳[1] 曾晓荣[2] 

机构地区：[1]四川泸州医学院附属医院心内科,646000 [2]四川泸州医学院附属医院心肌电生理研究室,646000

出　　处：《中华心血管病杂志》2005年第1期45-48,共4页Chinese Journal of Cardiology

基　　金：卫生部默沙东基金资助项目 (1997) ;四川省教育厅自然科学基金重点资助项目 (1996 16)

摘　　要：目的　探讨血管活性剂内皮素 1(ET 1)及前列腺素E1(PGE1)对高血压病患者肠系膜动脉平滑肌细胞钙激活钾 (KCa)通道活性的调控作用。方法　切取 2 1例老年高血压病患者及 18例老年非高血压者肠系膜动脉小分支节段 ,用酶消化法获取血管平滑肌细胞 ,以膜片钳技术检测KCa通道的活性 ,通过Pclamp专用软件实时采样记录其平均开放时间 (To) ,平均关闭时间 (Tc) ,平均开放概率 (Po)等。结果　 (1)高血压病患者KCa通道活性变化 ,于细胞内面向外膜片下 ,高血压病组与血压正常组比较 ,前者KCa通道Po增加 ,Tc延长 ,To缩短。在浴液中分别加入Ca2 + 后 ,两组KCa通道均被明显激活 ,与加Ca2 + 前比较 ,血压正常组Po的增加显著高于高血压病组 (P <0 0 0 1) ,说明高血压病组KCa通道对Ca2 + 的敏感性显著低于血压正常组。 (2 )两组溶液中加入ET 12～ 8× 10 9mol/L后 ,在内面向外式膜片下 ,血压正常组Po先增加后降低 ,Tc缩短 ,然而高血压病组患者肠系膜血管平滑肌KCa通道对ET 1则缺乏显著反应。 (3)溶液中加入PGE1后 ,在内面向外膜片下 ,高血压病患者血管平滑肌细胞KCa通道的通道电导增加 ,To显著延长 ,Tc显著缩短 ,Po显著增加 ,并呈浓度依赖性。结论　 (1)Objective To study regulation of Ca^2+-activated K+ channels (KCa) of mesenteric artery smooth muscle cell(SMC)from 21 old patients with essential hypertension (EH) by endothelin-1(ET-1)and prostagl E 1(PGE 1).Methods Mesenteric artery branch from EH was digested by enzyme. Patch clamp technique was used to pull cell-attached and inside-out patches on mesenteric artery SMC from EH and the normotensive patients respectively.The signal channel open probability (Po),open dwell-time(To) and close dwell- time(Tc),open channel number per patch were recorded.After adding Ca^2+ (10^-8～10^-6mol/L)、ET-1(2～8×109 mol/L) and PGE 1(10、20、40、100、200、400 nmol/L) to cytoplasm respectively.The parameters above were observed again.Results Compared to that of normotensive patients ,the activities of KCa channels of patients with EH was higher.After adding Ca^2+ to cytoplasm,the Po of KCa channels in normotensive patients increased significantly.But it was few changes in EH group.KCa channels has dual reaction to ET-1 in normotensive patients.We have found no statistics difference when ET-1 present on KCa channels of EH cases.Whereas PGE 1 can affect KCa channels current and channels kinetic significantly in side-out patches.The Po of KCa channels increased.The To protracted and the Tc curtailed in EH.Conclusions The activities of KCa channels of patients with EH increased significantly. but the sensitive to Ca^2+ decreased.ET-1 were few effect to KCa channels.The PGE 1 can activated KCa channels of patients with EH.

关 键 词：高血压病 患者 肠系膜动脉 血压正常 平滑肌细胞 PGE1 血管活性剂 Ca^2+ 外膜 通道 

分 类 号：R544.1[医药卫生—心血管疾病] R543[医药卫生—内科学]