Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and
renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous
system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II
via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting
enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its
important physiological roles, usually counterbalancing the classical effects exerted by Ang II.
Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the
brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of
Method: We carried out an extensive literature search in PubMed central.
Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions
that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity
and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts
effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for
instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis.
Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several
neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic
and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding
the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.