氯沙坦长期治疗对自发性高血压大鼠血管结构的影响

EFFECTS OF LOSARTAN ON THE STRUCTURE OF VESSEL IN SPONTANEOUSLY HYPERTENSIVE RATS

目的 :评价血管紧张素Ⅱ受体 1(AT1)拮抗剂氯沙坦 (Losartan)对自发性高血压大鼠 (SHR)血管结构的影响及在减缓高血压血管损害中的潜在作用 ,并探讨在高血压血管壁增厚的过程中醛固酮所起的作用。方法 :采用 10周龄SHR 16只 ,随机分为Losartan(SHRLOS)治疗组和对照组 (SHR) ,另选 10只同龄Wistar鼠作为正常对照。腹主动脉插管测定收缩压 ,应用计算机图像分析 ,计算血管中膜 /内径比 ,用光镜观察各组主动脉的结构变化 ;行肠系膜动脉离体灌注、反向高效液相 (HPLC)纯化和放免检测氯沙坦对血管局部合成醛固酮的影响。结果 :SHRLOS组收缩压 (SBP)与SHR组相比明显下降 (P =0 .0 0 1) ;其血管中膜 /内径比较SHR组显著降低 ,但仍高于Wistar组 ,血管壁结构接近Wistar组 ;SHRLOS组血管AngⅡ与SHR组无差异 ,醛固酮水平降至Wistar组。结论 :氯沙坦抑制血管合成醛固酮 ,逆转血管重构是其治疗高血压的机理之一。

Objective:To evaluate the potential actions of angiotensin Ⅱ receptor 1 (AT1)antagonist on systolic blood pressure,the structure of aorta and aldosterone of artery perfusion in spontaneously hypertensive rats.Methods:Ten weeks SHR were divided into two groups at random,with Wistar rats (n=10) as normal control.After 20 weeks treatment,the levels of systolic blood pressure and media wall to lume (W/L) were measured.By means of ex vivo mesenteric artery perfusion,HPLC and radioimmunoassay (RIA) aldoserone produced in the vasculature were quantified.Results:After 20 weeks treatment,the blood pressure of SHR los group was decreased compared with SHR;There were significant differences in W/L between SHR los and SHR,but SHR los group still remain in higher level than that of Wistar rats ( P <0.05).AngⅡ produced in mesenteric artery in SHR los group was not significantly changed compared with SHR control group,but the aldosterone was markedly lower to that of Wistar rats.Conclusion:Losartan is involved in the remedy of hypertensive vascular damage.