氯沙坦和依那普利对左旋硝基精氨酸诱导的高血压大鼠纤溶功能的影响  

Effect of Losartan and Enalapril on Frbrinolytic Function of L-N-Nitro-Arginine-induced Hypertensive Rats

作　　者：田洪森[1] 丁文惠[1] 彭旭[1] 王晓红[1] 唐朝枢[1] 

机构地区：[1]北京医科大学第一医院心内科,北京100034

出　　处：《中国动脉硬化杂志》2000年第2期147-150,共4页Chinese Journal of Arteriosclerosis

摘　　要：为探讨肾素 血管紧张素系统在纤溶功能紊乱中的意义 ;用腹腔注射左旋硝基精氨酸诱导大鼠高血压 ,导致纤溶功能紊乱 ,从第 2周开始分别给血管紧张素Ⅱ的 1型受体阻滞剂氯沙坦和血管紧张素转换酶抑制剂依那普利干预 ,于第 5周末应用发色底物法测定各组大鼠组织型纤溶酶原激活物及其抑制剂 1的血浆活性 ,并观察氯沙坦和依那普利干预的影响。结果发现 ,与对照组相比 ,高血压大鼠血浆纤溶酶原激活物抑制剂 1活性增强 5 0 % ,组织型纤溶酶原激活物活性减低 34% ,纤溶酶原激活物抑制剂 1与组织型纤溶酶原激活物的比值升高 12 7% ,差异均有显著性 (P <0 .0 1)。氯沙坦或依那普利干预均可使上述指标得到显著改善 (P <0 .0 1)。离体血管孵育时高血压大鼠血管释放纤溶酶原激活物抑制剂 1的能力比对照组明显增强 (P <0 .0 1) ;氯沙坦或依那普利干预使其生成纤溶酶原激活物抑制剂 1的基础水平及不同浓度凝血酶诱导的过度释放分别减少 19%～ 46 %和 2 5 %～ 5 0 % (P <0 .0 1) ,两种干预间差异无显著性 ;给 10 .0kIU L凝血酶刺激时 ,高血压大鼠离体血管组织型纤溶酶原激活物的生成较对照组下降 32 % (P <0 .0 5 ) ,氯沙坦和依那普利干预均未能改善这种下降趋势。结果表明 。Aim To investigate the role of reninangiotensin system (RAS) in the cause of fibrinolytic dysfunction. Methods 28 male Wistar rats were randomly divided into four groups: LNNA group: Wistar rats wre administered by intraperinoneol injection of LNNA (15 mg/kg everyday) to induce hypertensive model for 5 weeks; Losartan group and Enalapril group: the hypertensvie model were induced as LNNA group, and treated with losartan (10 mg/kg everyday) or enalapril (10 mg/kg everyday) by gavage from second to fifth week; 4) Control group: treated with normal saline and tap water instead of LNNA and losartan or enalapril in the same procedure. The activity changes of PAI1 and tPA both in plasma and in isolated vessls incubation were mearsured by spectrophotometric assay. Results Significant fibrinolytic dysfunction was found in the LNNA rats, and this dysfunction was markedly improved by the treatment with losartan or enalapril; Compared with the control group, the ability of PAI1 release in isolated vessels of LNNA rats was significantly increased (P<0.01). In the losartan and enalapriltreated group, the baseline levels and thrombininduced release of PAI1 in isolated vessels were reduced by 19%46% and 25%50% respectively (P<0.05), and there is no statistical difference between the two treatment groups. When induced by 10.0 kIU/L thrombin, the tPA release in isolated vessels of LNNA rats were 32% lower than that of controls (P<0.05), and this decline was not improved by the treatment with losartan and enalapril. Conclusions The regulation of RAS on fibrinolysis system is to accelerate the release of PAI1, which is mediated by Angiotensin Ⅱ.

关 键 词：氯沙坦 药理学 依那普利 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]