Physiological and pathophysiological functions of different angiotensins in the brain

The renin–angiotensin system (RAS) is better known for its role in the control of blood pressure, but evidence obtained from animal experiments and clinical trials suggests that it is involved in complex brain functions. It is now well accepted that neuronal AT 1 receptors mediate the stimulatory actions of angiotensin II regarding blood pressure and the intake of water and salt. In contrast, neuronal AT 2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic AT 1 receptors. Angiotensin‐(1‐7) [Ang‐(1‐7)] mediates its antihypertensive effects by stimulating synthesis and release of vasodilator prostaglandins and nitric oxide. New data concerning the receptor types binding angiotensin IV or Ang‐(1‐7) also support the existence of complex site‐specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Different angiotensin receptors (AT 1 , AT 2 , AT 4 , Mas) are also present in memory‐relevant structures. The effects of different angiotensins on cognition initiated the search for their mechanisms of action. Studies looking for a possible link between the RAS and brain disorders (stress, anxiety, depression, alcohol abuse, epilepsy, Alzheimer's disease) either inherited or acquired have been reviewed. The therapeutic potential of different angiotensins, as well as the potential use of agents known to influence the RAS, will be considered.