外渗
血脑屏障
氧化应激
血管紧张素II
炎症
活体显微镜检查
埃文斯蓝
血管通透性
医学
内分泌学
白细胞外渗
化学
内科学
磁导率
封堵器
药理学
紧密连接
内皮
免疫学
中枢神经系统
微循环
血压
作者
Ming Zhang,Y. J. Mao,Servio H. Ramirez,Ronald F. Tuma,T. Chabrashvili
出处
期刊:Neuroscience
[Elsevier]
日期:2010-12-15
卷期号:171 (3): 852-858
被引量:128
标识
DOI:10.1016/j.neuroscience.2010.09.029
摘要
Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte-endothelial interaction and blood-brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo, revealed a 4.2 fold (P<0.05, compared to vehicle) increase in leukocyte adhesion on day 4 of AngII infusion. This effect persisted through day 14 of AngII infusion, which resulted in a 2.6 fold (P<0.01, compared to vehicle) increase in leukocyte adhesion. Furthermore, evaluation of BBB permeability by Evans Blue extravasation showed that Ang II significantly affected the BBB, inducing 3.8 times (P<0.05, compared to vehicle) higher permeability. Previously we reported that AngII mediated hypertension promotes oxidative stress in the vasculature. Thus, we used the superoxide scavenger; 4-hydroxy-TEMPO (Tempol) to determine whether AngII via oxidative stress could contribute to higher leukocyte adhesion and increased BBB permeability. Tempol was given via drinking water (2 mmol) on day 4th following Ang II infusion, since oxidative stress increases in this model on day 4. Treatment with Tempol significantly attenuated the increased leukocyte/endothelial interactions and protected the BBB integrity on day 14 of AngII infusion. In conclusion, AngII via oxidative stress increases cerebral microvasculature inflammation and leads to greater immune-endothelial interaction and higher BBB permeability. This finding may open new avenues for the management of nervous system pathology involving cerebrovascular inflammation.
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