Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage.

Recent clinical studies have demonstrated that angiotensin II type 1 (AT(1) ) receptor blockers (ARBs) reduce the onset of stroke, stroke severity and the incidence and progression of Alzheimer's disease and dementia. We can expect that ARBs exert these effects by both AT(1) receptor blockade and angiotensin II type 2 (AT(2) ) receptor stimulation. Moreover, recent experimental results support the notion that AT(2) receptor stimulation with AT(1) receptor blockade could contribute to protection against ischaemic brain damage at least partly due to an increase in cerebral blood flow and decrease in oxidative stress, and prevent cognitive decline. Cellular therapy has been focused on as a new therapeutic approach to restore injured neurons. In this context, it has been reported that AT(2) receptor stimulation enhances neurite outgrowth and decreases neural damage, thereby enhancing neurogenesis. Moreover, additional beneficial effects of ARBs with an AT(1) receptor blocking action with a partial peroxisome proliferator-activated receptor (PPAR)-γ agonistic effect have been reported, and interaction of AT(2) receptor activation and PPAR-γ might be involved in these ARBs' effects. This article reviews the effects of regulation of activation of angiotensin II receptor subtypes on ischaemic brain damage and cognitive function, focusing on the effects of AT(2) receptor stimulation.