The depressor axis of the renin–angiotensin system and brain disorders: a translational approach

Abstract

All the components of the classic renin-angiotensin system (RAS) have been identified in the brain. Today, the RAS is considered to be composed mainly of two axes: the pressor axis, represented by angiotensin (Ang) II/angiotensin-converting enzyme/AT1 receptors, and the depressor and protective one, represented by Ang-(1-7)/ angiotensin-converting enzyme 2/Mas receptors. Although the RAS exerts a pivotal role on electrolyte homeostasis and blood pressure regulation, their components are also implicated in higher brain functions, including cognition, memory, anxiety and depression, and several neurological disorders. Overactivity of the pressor axis of the RAS has been implicated in stroke and several brain disorders, such as cognitive impairment, dementia, and Alzheimer or Parkinson's disease. The present review is focused on the role of the protective axis of the RAS in brain disorders beyond its effects on blood pressure regulation. Furthermore, the use of drugs targeting centrally RAS and its beneficial effects on brain disorders are also discussed.

Possible routes of SARS‐CoV‐2 invasion in brain: In context of neurological symptoms in COVID‐19 patients

“…A balanced RAS is crucial for neural homeostasis and its ACE2mediated dysregulation is implicated in neurodegenerative disorders (Gironacci, Vicario, Cerezo, & Silva, 2018).…”

How ACE inhibitors transformed the renin–angiotensin system

“…For the CNS, the blood–brain barrier ensures that the RAS located here is separated from the peripheral RAS and all the necessary substrates, enzymes, receptors and ligands are present in the CNS, along with the required control processes of stimulation or inhibition. The location of the RAS in the CNS has generated a new range of physiological and/or pharmacological target areas, including anxiety, learning, memory, physiological responses to stress and ischaemic stroke, apart from the centrally regulated effects on the peripheral cardiovascular system (Gebre, Altaye, Atey, Tuem, & Berhe, 2018; Gironacci, Vicario, Cerezo, & Silva, 2018; Santos et al, 2018).…”

Insights in Chloroquine Action: Perspectives and Implications in Malaria and COVID‐19

“…RAS is controlled by three major enzymes: (I) renin that cleaves angiotensinogen to originate angiotensin I (Ang I); (II) angiotensin‐converting enzyme (ACE) converting Ang I into angiotensin II (Ang II), whose actions are mediated by Ang II receptor type 1 (AT1R) and Ang II receptor type 2 (AT2R); (III) angiotensin‐converting enzyme 2 (ACE2), which hydrolyzes Ang II into Angiotensin‐(1‐7) (Ang 1–7) that exerts its biological function through the Mas receptor (Mas R) (49, 51). Then, the activity of ACE elevates Ang II concentration, whereas ACE2 catalyzes the cleavage of Ang II into Ang 1–7, characterizing the pressor axis (ACE/Ang II/AT1R) and the depressor axis (ACE2/Ang 1‐7/Mas R) (52), respectively. Alterations of activity and/or expression of one of these components cause an imbalance of RAS, hence, inducing cardiorespiratory problems.…”