Department of Molecular & Cellular Physiology Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Microcirculation. 2010 Nov;17(8):641-9. doi: 10.1111/j.1549-8719.2010.00060.x.
Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII (two week) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient (Rag-1(-/-) ) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES(-/-) and P-selectin(-/-) mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII.
血管紧张素 II（AngII）和 AngII 型 1 受体（AT1r）与高血压和缺血性中风的发病机制有关。本研究的目的是确定慢性 AngII 给药如何影响大脑微血管中的血脑屏障（BBB）功能和血细胞黏附。AngII 负载的渗透泵被植入野生型（WT）和突变型小鼠中。通过活体显微镜监测脑静脉中的白细胞和血小板黏附，并通过 Evans 蓝漏出检测 BBB 通透性。AngII（两周）输注增加了 WT 小鼠的血压。这伴随着 BBB 通透性增加和黏附的白细胞和血小板密度增加。AT1r（在血管壁上，但不在血细胞上）在很大程度上负责 AngII 对微血管的反应。免疫缺陷（Rag-1(-/-)）小鼠表现出白细胞募集反应减弱，而 BBB 通透性没有变化。RANTES(-/-) 和 P-选择素(-/-) 小鼠也出现了类似的保护模式，骨髓嵌合体（仅缺乏血细胞）的反应与各自的基因敲除相当。这些发现表明 AT1r 与 AngII 诱导的高血压相关的微血管功能障碍有关，并表明免疫细胞和与血细胞相关的 RANTES 和 P-选择素有助于 AngII 引起的血细胞募集，但不是 BBB 衰竭。
