氯沙坦对兔实验性动脉粥样硬化血管内皮的保护作用

目的　评估氯沙坦对高脂血症兔血管内皮的影响。方法　 5 0只日本♂长耳大白兔随机分为 5组 ,每组 10只。A组喂以含 1%胆固醇的兔饲料 ,B、C、D组在喂以含 1%胆固醇兔饲料的同时分别喂以 10mg·kg-1·d-1和 2 5mg·kg-1·d-1的氯沙坦以及 10mg·kg-1·d-1的开搏通 ,E组为正常对照组 ,喂以标准普通兔饲料 ,共 12wk。实验结束时 ,抽血对血脂水平进行测定。麻醉后处死动物 ,分离从主动脉根部至髂动脉分叉处的血管段 ,取主动脉弓处的组织行组织学检查 ;将胸主动脉切成 4mm长的血管环置浮槽中做离体实验 ,观察对乙酰胆碱、硝酸甘油、去甲肾上腺素的剂量反应曲线 ;剩余的血管制成组织匀浆 ,用放射免疫的方法对组织中的AngⅡ和ET 1进行测定。 结果　①A、B、C、D组的血脂和AngⅡ水平均明显高于E组 ,差异有显著性 (P <0 0 1) ;A、D组血管组织中ET 1水平明显高于B、C、E组 ,组间相比差异有显著性 (P <0 0 1) ;②A组的血管环对乙酰胆碱、硝酸甘油的舒张反应明显减弱 ,与E组相比差异有显著性 (P<0 0 1) ;B、C、D组与E组相比差异无显著性 (P >0 0 5 )。对去甲肾上腺素的缩血管效应在A、B组明显增强 (P <0 0 1) ,C、D组与E组相比差异无显著性 ;③各组的血管中膜面积相似 ;A、B、C、D组的血管横截面积明显增加 ,?

The protective effect of losartan on vascular endothelial cells for experimental atherosclerosis in rabbits

AIM The present study was designed to observed wether oral losartan would protect vascular endothelial cells in atherosclerotic aorta in rabbit induced by cholesterol diet. METHODS Fifty long ear Janpan white rabbits were randomly divided into five groups. Group E were fed standard diet, group A were fed choleterol diet, and group B, C and D were fed cholesterol diet and simultaneously received 10 mg·kg -1 ·d -1 ,25 mg·kg -1 ·d -1 of losartan and 10 mg·kg -1 ·d -1 of captopril respectively for 12 weeks. At the end of experiment, the rabbit blood samples were collected for measurement of the lipid profile. The rabbits were killed after dietary intervetion. The blood vessels was isolated from aorta to iliac artery, and adjacent to aortic arch were harvested for tissue review. While the thoracic aorta were cut into 4mm rings and mounted in organ bath for measurement of isometric force development. Dose response curve to acetylcholine, nitroglycerine, and noradrenaline were constructed. The rest tissue of made into tissue homogenate was used for measurement of the concentration of AngⅡ and ET 1. RESULTS ①The total lipid level in blood and AngⅡ level in tissue were significantly elevated in the rabbits fed cholesterol diet compared with that in groups E. The ET 1 level in tissue was significiantly elevated in group A and D compared with that in group B, C, and E( P <0 01). ② Endothelium dependent relaxation to acetylcholine and no endothe liumdependent relaxation to nitroglycerine were sinificiantly impaired in thoracic aorta rings in group A( P <0 01), but there no significiant difference in group B, C and D, compared with that in group E ( P >0 05). The constructive response to noradrenaline was significantly increased in group A and B, compared with that in group E ( P <0 01). However, these response in group C and D was similar to that in group E. ③ The media area was similar in each experimental group. The vessel area in group A, B, C, and D were enhanced significantly compared with that in group E ( P <0 05), the intima thick was enhanced and the lumen area was decreased significantly in group A compared with that in group E after intervention of the drugs, although the intima thick was significantly increased in group B, C, and D compared with that in group E, the lumen area were enhanced significantly compared with that in group A ( P <0 01). CONCLUSION In hypercholesterolmia, the concentration of AngⅡ in vessel tissues was increased significantly, and it maybe induced the vascular remodling and endothelial dysfunction via AT 1 receptor. AngⅡ type Ⅰreceptor antagonist, losartan has the protective effect on vascular endothelial cells and so delay the development of the atherosclerosis.