The renin angiotensin system in the central nervous system

Abstract

The first evidences indicating that angiotensin II (ANG II) was a peptide with action on the brain were shown in 1961 when it was found that the intraventricular injection of ANG II induces a centrally mediated pressor response (1). As a neuropeptide, ANG II belongs to the class of neuromodulators. The brain renin angiotensin system (RAS) exerts paracrine, autocrine and intracrine functions independently of circulating blood-borne ANG II which has a limited access to the brain by the blood-brain barrier (BBB) in the circumventricular organs (CVOs) (2). Brain-generated ANG II controls several physiological processes like stimulation of thirst, water intake and sodium appetite, acting as a neurotransmitter in neurons of brain areas such as the Subfornical organ (SFO) and Organum vasculosum of the lamina terminalis (OVLT). Generated angiotensins (ANGs) at the central nervous system (CNS) also stimulate endocrine secretions like argininevasopressin (AVP), oxytocin (OT), corticotrophin-releasing hormone (CRH) and adenocorticotrophin (ACTH secretion). Brain ANG II modulates the sympathetic autonomic functions and regulates blood pressure by increasing AVP and ACTH secretion and modulating the baroceptor reflex and the sympathetic output (3). During the last decade it has been established that, apart from its classical actions, ANG II exhibits other effects induced by direct action on its receptors or via local effects of its metabolites (4). Thereby, central actions of ANGs are not exclusively associated with their traditional roles. Indeed, several studies have shown that central ANGs are also involved in sexual behavior, stress, learning, and memory (5).