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慢性阻断血管紧张素Ⅱ1型受体不能完全防止模拟失重大鼠血管的适应性结构变化

高放, 张立藩, 黄威权, 孙岚

第四军医大学航空航天生理学教研室.陕西,西安 710032；第四军医大学组织与胚胎学教研室.陕西,西安 710032

摘要

作者以前的工作提示，在模拟失重所引起的血管区域特异性适应变化中，局部肾素--血管紧张素系统（local reninangiotensin system，L--RAS）可能发挥关键调控作用。该文以losartan慢性阻断血管紧张素Ⅱ1型受体（angiotensin Ⅱ typelreceptor，AT_(1)R），观察模拟失重是否仍能引起血管的这种适应性改变，并检测大血管管壁L--RAS主要成分的表达是否也发生相应变化。以尾部悬吊大鼠模型模拟失重的生理影响。制作基底动脉、胫前动脉、颈总动脉和腹主动脉的HE染色切片，在光学显微镜下进行形态观测：用免疫组织化学技米测量颈总动脉和腹主动脉壁的血管紧张素原（angiotensinogen，AGT）及AT_(1)R的表达变化。结果表明：4周模拟失重引起大鼠基底动脉中膜和颈总动脉管壁各平滑肌肌层肥厚，而胫前动脉和腹主动脉则发生萎缩性改变；给予losartan 4周引起上述4种血管皆发生萎缩性变化；阻断AT_(1)R，模拟失重仍然能引起基底动脉、颈总动脉发生相对肥厚性改变和腹主动脉萎缩加重。4周模拟失重还引起颈总动脉壁中AGT和AT_(1)R表达上调，而腹主动脉壁及血管周围组织中AGT和AT_(1)R表达下调；给予losartan 4周仅引起腹主动脉壁中AGT和AT_(1)R表达减少；阻断AT_(1)R，模拟失重使腹主动脉壁AT_(1)R表达进一步减少。结果提示，4周模拟失重引起大鼠脑、颈部与后身大、中动脉血管的形态结构改变和L--RAS主要成分表达发生上调或下调，血管L--RAS在其中可能发挥关键性调控作用；但在慢性阻断AT_(1)R的条件下，其它调控机制仍可能在脑血管适应性调节中发挥一定作用。

关键词： 失重; 血管紧张素原; 血管紧张素Ⅱ1型受体拮抗剂; 肾素-血管紧张素系统

Chronic blockade of angiotensin Ⅱ type 1 receptor cannot completely prevent structural adaptation in vessels of simulated weightless rats

Gao Fang, Zhang Lifan, Huang Weiquan, Sun Lan

Departments of Aerospace Physiology, The Fourth Military Medical University.Xi'an 710032,Shaanxi；China

Abstract

Our previous studies suggest that the vascular local renin-angiotensin system （L-RAS） plays a pivotal role in the region-specific vascular adaptation due to simulated weightlessness. The present study was designed to determine whether simulated weightlessness still induced adaptive changes in rat vessels when angiotensin Ⅱ type 1 receptor （AT_(1)R） was chronically blocked by the administration of losartan, and whether the expressions of key elements in the L-RAS in the large arteries would change. Tail suspension for 4 weeks was used to simulate the physiological effect of weightlessness. The responses of the basilar, anterior tibial, carotid arteries and abdominal aorta were observed by morphometric technique with light microscopy. The expressions of angiotensinogen （AGT） and AT_(1)R in the walls of common carotid artery and abdominal aorta were determined using immunohistochemical technique. The results showed that simulated weightlessness induced hypertrophy of the media of basilar artery and smooth muscle layers of carotid artery, but atrophic change in the anterior tibial artery and abdominal aorta. After 4 weeks of losartan treatment, all these arteries showed significant atrophic changes. However, simulated weightlessness still induced relative hypertrophy of the basilar artery and carotid artery and atrophy of the abdominal aorta when AT_(1)R was blocked. After 4 weeks of simulated weightlessness, the expressions of AGT and AT_(1)R were upregualted in The wall of carotid artery, but downregulated in the wall of abdominal aorta and perivascular tissues. Losartan decreased AGT and AT_(1)R expressions only in the wall of abdominal aorta; whereas simulated weightlessness further decreased AT_(1)R expression in the wall of abdominal aorta when AT_(1)R was blocked. We conclude that simulated weightlessness for 4 weeks still induces structural changes and upregulates or downregulates the key elements in L-RAS in the large and medium-sized arteries from fore and hind body parts of rats when AT_(1)R is blocked. The results suggest that the L-RAS in arterial tissue plays a pivotal role in these differential structural changes. However, there still exist other regulatory pathways to mediate the adaptive regulation of cerebral vessels when AT_(1)R is blocked.

Key words: weightlessness;angiotensinogen;angiotensinⅡtype 1 receptor antagonist;renin-angiotensin system

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引用本文：

高放, 张立藩, 黄威权, 孙岚. 慢性阻断血管紧张素Ⅱ1型受体不能完全防止模拟失重大鼠血管的适应性结构变化[J]. 生理学报 2007; 59 (6): 821-831.

Gao Fang, Zhang Lifan, Huang Weiquan, Sun Lan. Chronic blockade of angiotensin Ⅱ type 1 receptor cannot completely prevent structural adaptation in vessels of simulated weightless rats. Acta Physiol Sin 2007; 59 (6): 821-831 (in Chinese with English abstract).