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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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Citing This Article：

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).