The protective arms of the renin-angiotensin-system in neurological disease
In recent years it has been firmly established that apart from the classical renin-angiotensin-system (RAS) comprising angiotensin II (Ang II), angiotensin converting enzyme (ACE) - being responsible for Ang II generation - and the angiotensin type 1 receptor (AT1R), there also exist protective arms of the RAS which are the angiotensin type 2 receptor (AT2R) as well as angiotensin-(1-7) [Ang-(1-7)], angiotensin converting enzyme 2 (ACE2) - being mainly responsible for Ang-(1-7) synthesis - and the receptor for Ang-(1-7), Mas. AT2R stimulation 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 the AT2R 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 AT2R stimulation due - at least in part - to increased cerebral blood flow. There is indirect evidence that Ang 1-7 could play a role in protection against cognitive decline as well but respective studies are still to be awaited. In view of the data reviewed in this article, it can be assumed that the protective arms of the RAS are putative targets for the therapy of neurological diseases, which involve tissue damage or cognitive impairment. This article is protected by copyright. All rights reserved.
Clinical and Experimental Pharmacology and Physiology, 2013, Vol 40, Issue 8, p. 580-588