Protective arms of the renin-angiotensin-system in neurological disease

1. 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 AT(1) receptor (AT(1)R), there also exist protective arms of the RAS that comprise the angiotensin AT(2) receptor (AT(2)R), Ang-(1-7), ACE2 (mainly responsible for Ang-(1-7) synthesis) and Mas, the receptor for Ang-(1-7). 2. Stimulation of AT(2)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. 3. Stimulation of AT(2)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. 4. Cognitive function is improved by AT(2)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. 5. 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.