Abstract 32: Direct Angiotensin II Type 2 Receptor Stimulation by Compound 21 Prevents Vascular Dementia

Objectives: Recent clinical evidence demonstrated that angiotensin II type 1 receptor blockers (ARBs) were associated with a significant reduction in the incidence and progression of dementia compared with angiotensin converting enzyme inhibitor. Therefore, we examined the possibility that direct angiotensin II type 2 (AT2) receptor stimulation by AT2 receptor agonist, compound 21 (C21), could prevent cognitive decline associated with hypoperfusion in the brain. Methods: We employed a bilateral common carotid artery stenosis (BCAS) model in mice as a model of vascular dementia. The Morris water maze task was performed 6 weeks after BCAS operation. ARB, azilsartan (0.1 mg/kg/day) or C21 (10 μg/kg/day) was administered from 1 week before BCAS. Cerebral blood flow (CBF) was measured by laser speckle flowmetry and inflammatory cytokine levels were determined by real-time RT-PCR. Results: Wild-type (WT) mice showed the significant prolongation of escape latency after BCAS and this cognitive impairment was atte...