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

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.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.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.The renin-angiotensin system (RAS) has been implicated in the pathogenesis of different cardiovascular (CV) diseases, including stroke. Angiotensin II (Ang II), the principal effector molecule of the RAS, exerts some deleterious effects on the vasculature of different organ systems via its pressor properties and the resultant elevation of blood pressure. An additional component of the vascular dysfunction and tissue injury response mediated by Ang II has been attributed to the ability of the peptide to induce a pro-inflammatory, pro-thrombogenic, and pro-oxidative phenotype in both large and microscopic blood vessels [1-3]. Both the vasomotor and inflammatory effects of Ang II involve the activation of angiotensin II type 1 receptors (AT1R) that are expressed on leukocytes and platelets, endothelial cells an