氯沙坦对自发性高血压大鼠阻力血管结构的影响

Effects and Mechanisms of Losartan on the Structure of Resistant Vessel in Spontaneously Hypertensive Rat

目的 探讨氯沙坦 (Losartan)对自发性高血压大鼠 (SHR)阻力血管结构的影响 ,并观察在高血压血管壁增厚的过程中血管紧张素Ⅱ (AngⅡ )所起的作用。方法 采用 6周龄雄性SHR2 0只 ,随机分为Losartan治疗组(SHRlos)和对照组 (SHR)。另选同系雄性 6周龄WKY鼠 10只作为正常对照组。 6周龄SHRlos给予Losartan 30mg/kg/d ,溶于饮水灌胃治疗 17周。颈动脉插管 ,心电血流动力学监护仪测定动脉收缩压 ,应用计算机图象分析 ,计算血管壁腔面积比 ,用光镜和透射电镜观察SHR肠系膜动脉三级分支结构的变化 ;血浆放免法测肾素活性和AngⅡ含量。结果 (1)动脉收缩压 (SBP) :治疗结束后 ,SHRlos组血压与SHR组相比明显下降 ,差异有显著性 (P值 <0 0 5 )。 (2 )肠系膜动脉血管壁腔面积比和透射电镜观察 :SHRlos的血管壁腔面积比与SHR相比明显降低 ,差异有显著性 (P <0 0 1) ,与WKY相比 ,无显著性差异 (P >0 0 5 )。SHRlos的肠系膜超微结构与WKY相似 ,SHR的超微结构有异常改变。 (3)血浆肾素活性和AngⅡ水平 :血浆肾素活性在WKY和SHR之间无明显差异 (P >0 0 5 ) ,SHRlos肾素活性高于SHR(P值 <0 0 5 )SHRlos的AngⅡ水平高于SHR ,差异有显著性 (P <0 0 1)。SHRlos的AngⅡ高于WKY ,差异有显著性 (P <0 0 5 )。

Objective\ To evaluate the effects of Losartan on systolic blood pressure,the structure of resistant vessel and the changes of plasma angiotensinⅡ in spontaneously hypertensive rats (SHR). Methods\ six weeks male SHR and WKY were divided into three groups at random: SHR losartan group、SHR control group、WKY normal control group. Losartan 30 mg·kg 1 ·d 1 was administered by gavage to rats in SHR Losartan group. After 17 weeks treatment, Wall to lumen area ratios (W/L)of mesenteric arteries (3 rd grade branch ) were calculated by computer image analysis system. Systolic blood pressure(SBP) were measured. The level of vessel hypertrophy was assessed by means of transmission electron microscope. The plasma renin activity and AngⅡlevel was determined by RIA method. Results\ (1) After 17 weeks treatment, the blood pressure of SHR losartan group was decreased compared with SHR control group ( P <0 05). (2) The W/L in SHR losartan group was significantly decreased compared with SHR control group ( P <0 01). There was no remarkable difference in W/L between SHR losartan and WKY group( P >0 05).While the W/L in SHR losartan group is still remain in a higher level than that of WKY rats( P <0 05). The ultrastructures of mesenteric arteries in SHR losartan group were similar with those of WKY normal group; however, ultrastructure change in mesenteric arteries in SHR control group were pronouncedly. (3) The plasma renin activities had no significant differences ( P >0 05) between WKY normal group and SHR control group. The plasma renin activities in SHR losartan group increased compared with SHR control group ( P <0 05). AngⅡ level in SHR losartan group significantly increased compared with SHR control group ( P <0 01). The AngⅡ level in SHR losartan group was higher than that in WKY normal group ( P <0 05). Conclusion\ These results indicated that long term treatment with Losartan effectively reduced blood pressure、attenuated and regressed the resistant vessel hypertrophy during the development of hypertension in SHR.