氯沙坦(Losartan)逆转高血压大鼠血管壁超微结构的研究

Research of Reversal Effects of Losartan to the Ultrastrcture Lesion in Vascular Wall of SHR

目的 观察氯沙坦 (Losartan)对自发性高血压大鼠 (SHR)及正常对照组 (WKY)的淋巴细胞胞浆游离钙[Ca2 + ]i、血管紧张素Ⅱ (AngⅡ )水平和血管壁超微结构的影响及其降压效应 .方法 SHR 2 8只分为 3组 ,分别为 3月龄对照组 (SHR1)、6月龄对照组 (SHR2 )和Losartan治疗组 (SHR3 ) .治疗组从 3月龄开始予Losartan 2 0mg/kg/d治疗至 6月龄 .治疗前后检测鼠尾收缩压、淋巴细胞胞浆游离钙 [Ca2 + ]i、血浆AngⅡ和肠系膜动脉超微结构 .结果 Losartan对SHR有显著降压作用 .治疗前SHR的淋巴细胞钙 [Ca2 + ]i 水平均显著性增加 ,随鼠龄增大而加大 .肠系膜动脉出现明显血管壁损害 ,内皮细胞和平滑肌线粒体比表面均显著减少 ,而平滑肌细胞线粒体密度则显著增加 .经Losartan治疗后 ,在降压的同时淋巴细胞 [Ca2 + ]i 显著性下降 ,血管壁超微结构的损害得到明显逆转 .结论 高血压与血管平滑肌细胞存在的钙超负荷状态有关 ,并存在小动脉血管壁平滑肌和内皮细胞的超微结构损害 .Losartan能有效逆转血管平滑肌的钙超负荷状态 。

Objective To observe the effect in the process before and after treatment of Losartan in spontenously hypertensive rat (SHR) and controlled group(WKY) , and the changes of intralymphocytic calcium i,angiotensin Ⅱ(AngⅡ),and vascular wall ultrastructure. Methods 28 spontenously hypertensive rats (SHR) were randomly distributed to 3 groups: 3-month controlled group (SHR-1) ,6-month controlled group (SHR-2) ,and Losartan group (SHR-3). The 3-month age SHR from Losartan group were treated with Losartan (20mg/Kg/d) until the rats were 6-month age. Rat tail systolic press, lymphocyte cytosolic calcium ( i), ultrastructure of mesenteric artery ,plasma AngⅡwere measured before and after treatment. Results Losartan has a good hypertensive effect in SHRs. Level of AngⅡ,lymphocyte cytosolic calcium i increased in untreated SHRs. Those differences grow with the age increase. Vascular wall impairment appeared in untreated SHRs. Endothelial cells and mitochondrion specific surface significantly decreased. The volume density of mitochondrion in smooth muscle cells increased greatly. After treatment of Losartan, lymphocyte cytosolic calcium i decreased significantly and the impaired ultrastructure of vascular wall reversed. Conclusions Hypertension is related to over-loaded status of calcium in vascular smooth muscle cell. The ultrastructure impairment of arterial vascular smooth muscle and endothelial cell appeared. Losartan has reversal effects to over-loaded status of calcium in vascular smooth muscle and the ultrastuctural impairment of vascular wall.