厄贝沙坦对肾性高血压大鼠血管腺苷三磷酸酶活性和血管紧张素Ⅱ的影响  

Effects of Irbesartan on ATPase Activity and Angiotensin Ⅱ in Blood Vessel from Renal Hypertensive Rats

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

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

出　　处：《中华高血压杂志》2010年第4期370-374,共5页Chinese Journal of Hypertension

基　　金：贵州省优秀青年科技人才基金项目;贵州省科学技术基金重点项目[(2003)0316,(2002)3013]

摘　　要：目的探讨厄贝沙坦对肾性高血压大鼠(RHR)血管Na+-K+-腺苷三磷酸酶(ATPase)、Ca2+-ATPase和血管紧张素Ⅱ(AngⅡ)及血管重塑的影响。方法采用两肾一夹制造肾血管性高血压大鼠模型,18只造模成功的大鼠随机分为RHR组、厄贝沙坦组[50 mg/(kg.d)]、停药组[厄贝沙坦50 mg/(kg.d)灌胃7周后停药1周],每组6只。另设一假手术组(n=6)。测量各组大鼠用药前后血压;8周后,测量大鼠胸主动脉及肠系膜动脉血管壁厚度;采用酶学比色法检测Na+-K+-ATPase、Ca2+-ATPase活性;采用放射免疫技术检测血浆、肠系膜动脉及胸主动脉局部AngⅡ水平。结果与假手术组比较,RHR血压显著升高,血管壁厚度明显增厚,血浆及血管组织AngⅡ明显升高,血管Na+-K+-ATPase、Ca2+-ATPase活性降低;与RHR组比较,厄贝沙坦组大鼠血压明显降低,肠系膜动脉血管壁厚度明显减轻,胸主动脉、肠系膜动脉AngⅡ水平及Ca2+-ATPase活性均升高,Na+-K+-ATPase活性无明显变化;与厄贝沙坦组比较,停药组血压明显升高,胸主动脉及肠系膜动脉Ca2+-ATPase活性明显降低,Na+-K+-ATPase活性无变化。RHR血管Ca2+-ATPase活性与局部AngⅡ呈负相关。结论RHR血管重塑与血管组织ATPase活性降低、AngⅡ升高有关,厄贝沙坦逆转血管重塑的作用可能部分与Ca2+-ATPase活性增加有关。Objective To explore the effects of Irbesartan on activities of Na^＋-K^＋-ATPase,Ca^2＋-ATPase,Angiotensin Ⅱ（Ang Ⅱ）and vascular remodeling in renal hypertensive rats（RHR）.Methods Renovascular hypertension was induced by two kidney-one clip method.Eighteen RHR were randomly divided into 3 groups： RHR model group（n=6）,Irbesartan treated group [50 mg/（kg·d）,n=6],withdrawal group（n=6）.Six rats were included in sham operation group.Blood pressure（BP） was measured before and after using irbesartan.Thicknesses of vascular wall（TVW） of thoracic aorta and mesenteric artery were measured after 8 weeks.ATPase activities were determined by enzymatic colorimetric method.Ang Ⅱ level was determined by radioimmunoassay.ResultsCompared to the sham operation group,BP,TVW,Ang Ⅱ of plasma and blood vessel were increased in RHR.The activities of Na^＋-K^＋-ATPase,Ca^2＋-ATPase were decreased in RHR.BP,TVW of mesenteric artery were significantly decreased by irbesartan treatment.An increased Ang Ⅱ level and activity of Ca^2＋-ATPase in thoracic aorta and mesenteric artery was also found.No change the activity of Na^＋-K^＋-ATPase was found after irbesartan treatment.One week after discontinuation of treatment,BP was significantly elevated,the activity of Ca^2＋-ATPase of thoracic aorta was decreased（both P0.01）,There was a significant negative correlation between Ang Ⅱ and the activity of Ca^2＋-ATPase in RHR.Conclusion The vascular remodeling of RHR may be associated with decreased vascular ATPases activities.Irbesartan can reverse vascular remodeling partially by increasing Ca^2＋-ATPase activity.

关 键 词：腺苷三磷酸酶 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]