Overactivity of the renin-angiotensin system (RAS) is involved in the pathogenesis of Hypertension and a hyper-functioning brain RAS has been highlighted in several genetic and experimental models. Until now, Angiotensin (Ang)-II was thought to be the main actor of this system and the ACE/Ang-II/AT1 receptor axis was the main target for antihypertensive therapies. A new member of the RAS, ACE2 (angiotensin converting enzyme type 2) has been identified in organs and tissues related to cardiovascular function (e.g. heart, kidney, vessels) and appears to be part of a counter-regulatory pathway buffering the excess of Ang-II. We recently identified the ACE2 protein in brain regions involved in the central regulation of blood pressure (BP) and showed that it regulates, and is regulated by, other components of the RAS. Here, we present evidence for brain ACE2’s involvement in the central regulation of BP, autonomic and cardiac function. We show that lack of ACE2 is deleterious for the central regulation of BP and that brain ACE2 gene therapy can restore baroreflex and autonomic functions and prevent the development of Hypertension. Additionally, and independently of Ang-II levels reduction, we will highlight some of the mechanisms responsible for the beneficial effects of central ACE2 in cardiovascular function.
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