肾性高血压大鼠脑ATP酶活性和血管紧张素Ⅱ水平及厄贝沙坦的干预  

Effects of Irbesartan on changes of ATPase activity and AngⅡ in brain of renal hypertensive rats

作　　者：吴泽兵[1] 商黔惠[2,3] 姜黔峰[2,3] 吴芹[4] 袁萍[2,3] 

机构地区：[1]合肥市第一人民医院干部病房 [2]遵义医学院临床医学研究所 [3]遵义医学院附属医院心血管内科,贵州遵义563003 [4]遵义医学院药理教研室

出　　处：《中国老年学杂志》2011年第18期3533-3535,共3页Chinese Journal of Gerontology

基　　金：贵州省优秀科技教育人才省长专项基金项目(2005239);贵州省科学技术基金重点项目(20023013)

摘　　要：目的探讨厄贝沙坦对肾性高血压大鼠(RHR)脑Na+,K+-ATPase、Ca2+-ATPase及血管紧张素Ⅱ(AngⅡ)的影响。方法采用两肾一夹制造肾血管性高血压模型,18只造模成功的RHR随机分为模型组(RHR)、厄贝沙坦组(50 mg.kg-1.d-1)、停药组,另设假手术组对照,每组6只,测量各组大鼠用药前后血压;用药8 w后,分别用生化酶学方法和放射免疫技术检测大鼠大脑皮质、海马Na+,K+-ATPase、Ca2+-ATPase活性及AngⅡ水平。结果 RHR血压〔(189±15)mmHg〕明显高于对照组〔(134±9)mmHg〕;厄贝沙坦治疗后,血压明显下降〔(123±7)mmHg〕,停药后,血压明显上升〔(154±10)mmHg〕。与假手术组比较,RHR大脑皮质、海马Na+,K+-ATPase、Ca2+-ATPase活性明显降低。厄贝沙坦对Na+,K+-ATPase活性无明显影响,但能明显升高Ca2+-ATPase活性,停药后Ca2+-ATPase活性明显下降。厄贝沙坦能明显升高血浆、大脑皮质、海马的AngⅡ水平,停药后血浆AngⅡ水平无明显改变,大脑皮质、海马的AngⅡ水平明显下降。RHR脑Ca2+-ATPase与局部AngⅡ水平呈显著负相关。结论厄贝沙坦影响RHR脑Ca2+-ATPase活性及AngⅡ水平,Ca2+-ATPase活性降低可能与局部AngⅡ升高有关。停药后循环和大脑局部AngⅡ及Ca2+-ATPase活性变化,可能是高血压反跳的机制之一。Objective To explore the effects of Irbesartan on the activities of Na ＋,K ＋-ATPase,Ca 2 ＋-ATPase and the level of AngiotensinⅡ（AngⅡ） in brain of renal hypertensive rats（RHRs）.Methods Renovascular hypertension was induced by two kidney-one clip method.Eighteen renovascular hypertensive rats were randomly divided into RHR Model,Irbesartan treated（50 mg.kg-1.d-1）,and discontinuation groups,each group had 6 cases.Blood pressure（BP） was measured before and after using irbesartan.ATPase activity and Ang Ⅱ content were determined by spectrophotometry or radioimmunoassay in the cerebral cortex and hippocampus from RHR after 8 week treatment.Results Blood pressure of RHR was significantly higher than that of control group,Irbesartan significantly decreased blood pressure of RHR.The activities of Na ＋,K ＋-ATPase,Ca 2 ＋-ATPase in cerebral cortex and hippocampus from RHR were significantly lower than those of control group（P 0.01）;Irbesartan did not change the activity of Na ＋,K ＋-ATPase,but significantly increased the activity of Ca 2 ＋-ATPase.Ca 2 ＋-ATPase activity was decreased after discontinuation.The plasma and brain AngⅡ level of RHR was significantly higher than those of control group,Irbesartan increased AngⅡ level of plasma,cerebral cortex and hippocampus of RHR.After discontinuation,AngⅡ level of plasma had no evident alteration,AngⅡ level of cerebral cortex and hippocampus of RHR were significantly decreased.There was a significant negative correlation between AngⅡ and the activity of Ca 2 ＋-ATPase in RHR brain.Conclusions Irbesartan may impact on the activity of Ca 2 ＋-ATPase and the level of AngⅡ in RHR brain,and the decreased Ca 2 ＋-ATPase activity may be related to local increased AngⅡ,which might be one of the mechanisms of the rebound of hypertension.

关 键 词：ATP酶 血管紧张素Ⅱ 厄贝沙坦 高血压 肾性 大鼠 

分 类 号：R544.1[医药卫生—心血管疾病]