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

Recent clinical studies have demonstrated that angiotensin II type 1 (AT1) 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 AT1 receptor blockade and angiotensin II type 2 (AT2) receptor stimulation. Moreover, recent experimental results support the notion that AT2 receptor stimulation with AT1 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 AT2 receptor stimulation enhances neurite outgrowth and decreases neural damage, thereby enhancing neurogenesis. Moreover, additional beneficial effects of ARBs with an AT1 receptor blocking action with a partial peroxisome proliferator‐activated receptor (PPAR)‐γ agonistic effect have been reported, and interaction of AT2 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 AT2 receptor stimulation. LINKED ARTICLES This article is one of a set of reviews submitted to BJP in connection with talks given at the September 2010 meeting of the International Society of Hypertension in Vancouver, Canada. To view the other articles in this collection visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01235.x, http://dx.doi.org/10.1111/j.1476‐5381.2011.01260.x and http://dx.doi.org/10.1111/j.1476‐5381.2011.01366.x