Anti-inflammatory effects of angiotensin receptor blockers in the brain and the periphery.
Anti-inflammatory effects of angiotensin receptor blockers in the brain and the periphery.
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DOI：
10.1007/s10571-009-9368-4
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发表时间：
2009-09
影响因子：
4
通讯作者：
Saavedra, Juan M.
中科院分区：
文献类型：
--
作者：
Benicky, Julius;Sanchez-Lemus, Enrique;Pavel, Jaroslav;Saavedra, Juan M.
除了调节血压外，血管紧张素II通过刺激其AT 1受体在高血压中发挥强大的促炎作用，在外周动脉和脑血管中最清楚地证明。血管紧张素II受体阻滞剂（ARB）的给药可减少外周器官中高血压相关的血管炎症。在遗传性高血压的啮齿动物模型中，ARB逆转了大脑微循环中的炎症。我们假设ARB对高血压以外的炎症性疾病也有效。我们最近的研究表明，情况确实如此。我们使用细菌内毒素脂多糖（LPS）的全身给药模型。LPS在外周器官和大脑中产生强烈的初始炎症反应，即先天免疫反应。ARB坎地沙坦预处理可显著降低对LPS的反应，包括减少促炎细胞因子释放至全身循环，减少促炎肾上腺激素醛固酮的产生和释放。此外，ARB非常显著地降低了LPS诱导的促炎细胞因子的基因表达和脑中小胶质细胞的活化。我们的研究结果表明，AT1受体活性是必不可少的不受限制的发展，全面的先天性免疫反应在外周和大脑。ARB由于其免疫反应限制特性，可被认为在外周器官和大脑的许多炎性疾病中具有治疗作用。
In addition to regulating blood pressure, Angiotensin II exerts powerful pro-inflammatory effects in hypertension through stimulation of its AT1 receptors, most clearly demonstrated in peripheral arteries and in the cerebral vasculature. Administration of Angiotensin II receptor blockers (ARBs) decreases hypertension-related vascular inflammation in peripheral organs. In rodent models of genetic hypertension, ARBs reverse the inflammation in the cerebral microcirculation. We hypothesized that ARBs could be effective in inflammatory conditions beyond hypertension. Our more recent studies, summarized here, indicate that this is indeed the case. We used the model of systemic administration of the bacterial endotoxin lipopolysaccharide (LPS). LPS produces a robust initial inflammatory reaction, the innate immune response, in peripheral organs and in the brain. Pretreatment with the ARB candesartan significantly diminishes the response to LPS, including reduction of pro-inflammatory cytokine release to the general circulation and decreased production and release of the pro-inflammatory adrenal hormone aldosterone. In addition, the ARB very significantly decreased the LPS-induced gene expression of pro-inflammatory cytokines and microglia activation in the brain. Our results demonstrate that AT1 receptor activity is essential for the unrestricted development of full-scale innate immune response in the periphery and in the brain. ARBs, due to their immune response-limiting properties, may be considered as therapeutically useful in a number of inflammatory diseases of the peripheral organs and the brain.
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影响因子：
5.3
作者：
Ching, San;Zhang, Hao;Quan, Ning
通讯作者：
Quan, Ning
DOI：
10.1080/10253890801892040
发表时间：
2008-01-01
影响因子：
2.3
作者：
Bregonzio, C.;Seltzer, A.;Saavedra, J. M.
通讯作者：
Saavedra, J. M.
影响因子：
4.9
作者：
Dahlöf, Björn
通讯作者：
Dahlöf, Björn
影响因子：
8.3
作者：
Ito, T;Yamakawa, H;Saavedra, JM
通讯作者：
Saavedra, JM
影响因子：
4.8
作者：
Laflamme, N;Rivest, S
通讯作者：
Rivest, S