Gao Fang, Zhang Li-Fan, Huang Wei-Quan, Sun Lan
Department of Aerospace Physiology, The Fourth Military Medical University, Xi'an 710032, China.
Sheng Li Xue Bao. 2007 Dec 25;59(6):821-30.
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.
我们之前的研究表明，血管局部肾素-血管紧张素系统（L-RAS）在模拟失重引起的区域特异性血管适应中起关键作用。本研究旨在确定当通过给予氯沙坦长期阻断1型血管紧张素II受体（AT(1)R）时，模拟失重是否仍会诱导大鼠血管发生适应性变化，以及大动脉中L-RAS关键元件的表达是否会改变。采用尾部悬吊4周来模拟失重的生理效应。用光学显微镜形态计量技术观察基底动脉、胫前动脉、颈动脉和腹主动脉的反应。用免疫组织化学技术测定颈总动脉和腹主动脉壁中血管紧张素原（AGT）和AT(1)R的表达。结果显示，模拟失重诱导基底动脉中膜和颈动脉平滑肌层肥大，但胫前动脉和腹主动脉出现萎缩性变化。氯沙坦治疗4周后，所有这些动脉均出现明显的萎缩性变化。然而，当AT(1)R被阻断时，模拟失重仍会诱导基底动脉和颈动脉相对肥大以及腹主动脉萎缩。模拟失重4周后，颈动脉壁中AGT和AT(1)R的表达上调，但腹主动脉壁和血管周围组织中的表达下调。氯沙坦仅降低腹主动脉壁中AGT和AT(1)R的表达；而当AT(1)R被阻断时，模拟失重进一步降低腹主动脉壁中AT(1)R的表达。我们得出结论，当AT(1)R被阻断时，4周的模拟失重仍会诱导大鼠前后身体部位大中型动脉的结构变化，并上调或下调L-RAS中的关键元件。结果表明，动脉组织中的L-RAS在这些不同的结构变化中起关键作用。然而，当AT(1)R被阻断时，仍存在其他调节途径来介导脑血管的适应性调节。
