Role of blood cell-associated angiotensin II type 1 receptors in the cerebral microvascular response to ischemic stroke during angiotensin-induced hypertension

Experimental & Translational Stroke Medicine

D Neil Granger¹  Gokhan Yilmaz¹  Stephen F Rodrigues¹  Shantel A Vital¹  Satoshi Terao¹  Mutsumi Nagai¹ 

[1] Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA

关键词: inflammation;    cerebral ischemia;    bone marrow chimera;    blood brain barrier;    angiotensin II type 1 receptor;   

Others  :  862010
DOI  :  10.1186/2040-7378-3-15

 received in 2011-10-17, accepted in 2011-11-16,  发布年份 2011

【 摘 要 】

Background

Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension.

Methods

The contributions of BC- and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR^-/-, and bone marrow chimera mice with either a BC+/EC+ (WT→WT) or BC-/EC+ (AT1aR^-/-→WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice.

Results

The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR^-/- mice. A similar level of protection was noted in AT1aR^-/- →WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively.

Conclusions

BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II-hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R.

【 授权许可】

   
2011 Nagai et al; licensee BioMed Central Ltd.

【 图 表 】

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