Abstract: The renin-angiotensin system (RAS) was originally conceived as a circulating hormonal system involved in the regulation of cardiovascular and renal homeostasis. With the discovery of local RAS components in diverse organs, including the brain, and related biologically active peptides, enzymes, and receptors, the understanding of the physiological and pathophysiological roles of RAS has changed significantly. Accordingly, RAS has been conceptualized as a system composed of two major axes: a “classical” one formed by the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and angiotensin type 1 (AT1) receptor (ACE/Ang II/AT1), and a ‘counter-regulatory’ one composed by the ACE2, Ang-(1-7), Mas receptor (ACE2/Ang-(1-7)/Mas). The classical arm promotes vasoconstriction, pro-inflammatory, pro-thrombotic, and pro-fibrotic effects mainly through the activation of AT1 receptors. Ang II can also bind to AT type 2 receptor but with much less affinity and with distinct effects of AT1. The counter-regulatory axis ACE2/Ang-(1-7)/Mas often opposes the actions of the classical arm, promoting anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-fibrotic effects (Miranda et al., 2022).