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高血压对大鼠脑基底动脉收缩和钠泵活性的影响 预览 被引量:3

Effect of hypertension on vascular contraction and sodium pump activity in rat cerebral basilar artery
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摘要 目的探讨高血压对大鼠脑血管收缩性的影响及其与钠泵活性的关系。方法取♂Wistar大鼠(WR)和自发性高血压大鼠(SHR)基底动脉环,通过Multi Myograph张力换能系统记录血管张力变化,比较两种大鼠离体脑动脉对KCl和5-羟色胺(5-HT)的收缩反应,分析高血压病变对脑血管收缩性和钠泵活性的影响。结果与WR基底动脉相比,SHR基底动脉的KCl和5-HT量效曲线明显右移,再复K+所致血管舒张作用减弱,提示高血压病变可明显降低脑血管钠泵活性及KCl和5-HT的收缩反应;哇巴因(Ouabain,OUA)浓度依赖性收缩SHR脑血管,其量效关系曲线可经两点结合模型进行最佳拟合,Kd分别为:1.7×10~(-8)mol·L~(-1)和1.6×10~(-5)mol·L~(-1),表明SHR脑基底动脉上存在高、低亲和力两种不同功能的钠泵。用5×10~(-7)mol·L~(-1)和10~(-4)mol·L~(-1)的OUA分别抑制高、低亲和力钠泵,仅能在SHR而非WR脑血管明显左移KCl和5-HT量效曲线,表明OUA可明显增强KCl和5-HT对脑血管的收缩作用,且OUA增强5-HT收缩SHR脑血管的作用呈明显的浓度依赖性(r=0.9393,P〈0.05);在SHR脑血管,这两个浓度OUA对KCl量效曲线的左移幅度无明显差别,而对5-HT收缩量效曲线的左移幅度却有明显不同,提示仅高亲和力钠泵介导了SHR脑血管对KCl的收缩反应,而SHR脑血管对5-HT的收缩反应则由高、低亲和力两种钠泵共同参与。结论高血压病变可明显降低脑血管对血管收缩剂的反应性,其机制可能与高血压所致钠泵活性降低或钠泵对OUA敏感性增加有关。 Aim To explore the effects of hypertension on the contractibility of rat basilar artery and its interactions with the sodium pump activity. Methods The basilar artery was respectively isolated from Wistar and SHR rats,and the isometric tension of arterial rings was measured by Multi Myograph System-610 M. The contractibilities of arterial rings induced by KCl or 5-HT were compared between the basilar arteries of the two groups of rats to analyze the effect of hypertension on the cerebral vascular tension and the activity of sodium pump. Results In SHR rats,the concentration-response curves of the contraction of isolated basilar artery rings induced by KCl and 5-HT were significantly shifted to right,and the relaxation of vascular tone induced by K+which was reintroduced from the external was attenuated compared with those in the WR. These results suggested that hypertension could significantly decrease the activity of the sodium pump and the contractile responses of KCl and 5-HT. OUA could contract the basilar artery in a concentration-dependent manner,and its concentration-response curve was optimally fitted by a two-site binding model: Kd was 1. 7× 10~(-8)and 1. 6 × 10~(-5)mol·L~(-1),respectively. The results indicated that the two different function sodium pumps existed in the rat basilar artery: one with the high OUA affinity and the other with the low OUA affinity. If the high and low affinity sodium pumps were inhibited by 5 × 10~(-7)and 10~(-4)mol·L~(-1)OUA,respectively,the concentration-response curves of KCl and 5-HT would shift to left in SHR rats but not in WR rats. It suggested that OUA could enhance the contraction induced by KCl and 5-HT significantly,and a concentration-dependent effect was observed in the SHR vascular contraction induced by 5-HT( r =0. 9393,P 0. 05). When the two concentrations of OUA were applied,there was no significant difference in the shift left of the concentration-response curves induced by KCl in the SHR cerebral vessels. However,the
作者 王海燕 郝亮 郭宇松 王永利 郭炜 WANG Hai- yan1, HAO Liang1, GUO Y u - song1, WANG Yong- li 2, GUO Wei2 (1. Dept of P h a rm a c y, the Third Hospital o f S hi j ia zh u a n g, 2. School o f P h a rm a c y, Hebei Medical University, Shi jiazhuang 050017,China)
出处 《中国药理学通报》 CAS CSCD 北大核心 2017年第1期74-83,共10页 Chinese Pharmacological Bulletin
关键词 高血压 基底动脉 血管收缩 KCL 5-HT 哇巴因 钠泵 hypertension basilar artery vascular contraction KCl 5-HT OUA sodium pump
作者简介 王海燕(1982-),女,硕士,主管药师,研究方向:药理学,E-mail:carinawang@163.com; 郭炜(1979-),女,博士,副教授,研究方向:药代动力学,通讯作者,E-mail:guowei8043586@sina.com
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