【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。更多还原

【Abstract】 Objective To explore the effects of Irbesartan on activities of Na+-K+-ATPase,Ca2+-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,Ca2+-ATPase were decreased in RHR.BP,TVW of mesenteric artery were significantly decreased by irbesartan treatment.An increased Ang Ⅱ level and activity of Ca2+-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 Ca2+-ATPase of thoracic aorta was decreased(both P<0.01),There was a significant negative correlation between Ang Ⅱ and the activity of Ca2+-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 Ca2+-ATPase activity.更多还原