title: Protective arms of the renin-angiotensin-system in neurological disease.
abstract: In recent years it has been firmly established that apart from the classic renin-angiotensin system (RAS) comprising angiotensin (Ang) II, angiotensin converting enzyme (ACE; responsible for AngII generation) and the angiotensin AT1 receptor (AT1 R), there also exist protective arms of the RAS that comprise the angiotensin AT2 receptor (AT2 R), Ang-(1-7), ACE2 (mainly responsible for Ang-(1-7) synthesis) and Mas, the receptor for Ang-(1-7).  Stimulation of AT2 R promotes neuronal differentiation, neurite outgrowth and axonal regeneration, which results in an acceleration of repair and improved functional outcome after injury of peripheral nerves or the spinal cord.  Stimulation of AT2 R and the receptor Mas has been shown to reduce infarct size and ameliorate neurological deficits in various animal models of stroke. The underlying mechanisms of action are comprised of activation of direct neurotrophic, anti-inflammatory and anti-oxidant pathways, as well as the augmentation of cerebral blood flow.  Cognitive function is improved by AT2 R stimulation due, at least in part, to increased cerebral blood flow. There is indirect evidence that Ang-(1-7) could also play a role in protection against cognitive decline, but studies confirming this have not yet been published.  In view of the data reviewed in this article, it can be assumed that the protective arms of the RAS are putative targets in the treatment of neurological diseases, which involve tissue damage or cognitive impairment.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Robert E
authors.initials: RE
authors.lastname: Widdop
authors.forename: Claudia
authors.initials: C
authors.lastname: McCarthy
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Ulrike M
authors.initials: UM
authors.lastname: Steckelings
mesh_terms: D002493:Central Nervous System Diseases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D044139:Receptor, Angiotensin, Type 2
keywords: AT2 receptor; angiotensin-(1-7) receptor; angiotensin-converting enzyme 2; cognitive disorders; receptor Mas; renin-angiotensin-system; stroke