Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.
Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.
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DOI：
10.1016/j.psyneuen.2010.10.001
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发表时间：
2011-01
影响因子：
3.7
通讯作者：
Benicky, Julius
中科院分区：
文献类型：
--
作者：
Saavedra, Juan M.;Sanchez-Lemus, Enrique;Benicky, Julius
关键词：
对压力的不良适应、脑血管功能的改变和过度的脑炎症在许多精神和神经障碍的病理生理学中起关键作用，所述精神和神经障碍例如重性抑郁症、精神分裂症、创伤后应激障碍、帕金森病和阿尔茨海默病以及创伤性脑损伤。目前，对这些高度流行和破坏性疾病的治疗非常有限，而且很多时候效率低下，寻找新的治疗方案至关重要。最近，人们的注意力集中在脑调节肽血管紧张素II的作用及其生理AT 1受体阻断的翻译价值上。除了其众所周知的心血管效应之外，血管紧张素II通过AT 1受体刺激是一种多效性脑调节因子，参与控制对应激的反应、调节脑血管流量和对炎症的反应。过度的脑AT 1受体活性与对压力的过度交感神经和激素反应、对脑血管缺血和脑炎症的脆弱性、导致神经元损伤的过程相关。在动物模型中，全身给予血管紧张素II受体阻滞剂抑制脑AT 1受体活性具有神经保护作用;它减少过度的应激反应和焦虑，预防应激诱导的胃溃疡，降低缺血和中风的易感性，逆转慢性脑血管炎症，并减少细菌内毒素产生的急性炎症反应。这些作用保护神经元免受损伤，并有助于延长寿命。血管紧张素II受体阻滞剂是广泛用于治疗高血压的具有良好安全范围的化合物，其抗炎和血管保护作用有助于减少肾和心血管衰竭。抑制人类大脑AT 1受体也具有神经保护作用，可降低中风的发生率，改善认知能力并减缓阿尔茨海默病的进展。阻断AT 1受体为治疗日益增加的患病率和社会经济影响的疾病提供了一种新的安全的治疗方法，如情绪障碍和大脑神经退行性疾病。
Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT1 receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT1 receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT1 receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT1 receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT1 receptors in humans is also neuroprotective, reducing the incidence of stroke, improving cognition and decreasing the progression of Alzheimer's disease. Blockade of AT1 receptors offers a novel and safe therapeutic approach for the treatment of illnesses of increasing prevalence and socioeconomic impact, such as mood disorders and neurodegenerative diseases of the brain.
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影响因子：
4
作者：
Benicky, Julius;Sanchez-Lemus, Enrique;Pavel, Jaroslav;Saavedra, Juan M.
通讯作者：
Saavedra, Juan M.
影响因子：
13.5
作者：
Cuadra AE;Shan Z;Sumners C;Raizada MK
通讯作者：
Raizada MK
影响因子：
3.2
作者：
Chrysant, Steven G.
通讯作者：
Chrysant, Steven G.
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.
DOI：
10.1073/pnas.86.2.725
发表时间：
1989-01-01
影响因子：
11.1
作者：
CASTREN, E;SAAVEDRA, JM
通讯作者：
SAAVEDRA, JM