The goal of the present review is to examine the evidence for beneficial actions of manipulation of the RAS (renin–angiotensin system) in stroke, with particular focus on Ang-(1–7) [angiotensin-(1–7)] and its receptor Mas. The RAS appears to be highly involved in the multifactorial pathophysiology of stroke. Blocking the effects of AngII (angiotensin II) at AT1R (AngII type 1 receptor), through the use of commonly prescribed ACE (angiotensin-converting enzyme) inhibitors or AT1R blockers, has been shown to have therapeutic effects in both ischaemic and haemorrhagic stroke. In contrast with the deleterious actions of over activation of AT1R by AngII, stimulation of AT2Rs (AngII type 2 receptors) in the brain has been demonstrated to elicit beneficial effects in stroke. Likewise, the ACE2/Ang-(1–7)/Mas axis of the RAS has been shown to have therapeutic effects in stroke when activated, countering the effects of the ACE/AngII/AT1R axis. Studies have demonstrated that activating this axis in the brain elicits beneficial cerebral effects in rat models of ischaemic stroke, and we have also demonstrated the cerebroprotective potential of this axis in haemorrhagic stroke using stroke-prone spontaneously hypertensive rats and collagenase-induced striatal haemorrhage. The mechanism of cerebroprotection elicited by ACE2/Ang-(1–7)/Mas activation includes anti-inflammatory effects within the brain parenchyma. The major hurdle to overcome in translating these results to humans is devising strategies to activate the ACE2/Ang-(1–7)/Mas cerebroprotective axis using post-stroke treatments that can be administered non-invasively.
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Review Article| October 01 2013
Cerebroprotective action of angiotensin peptides in stroke
Robert W. Regenhardt;
Douglas M. Bennion;
*Department of Physiology and Functional Genomics and McKnight Brain Institute, University of Florida, 1600 SW Archer Road, PO Box 100274, Gainesville, FL 32610-0274, U.S.A.
Correspondence: Dr Colin Sumners (email email@example.com).
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Robert W. Regenhardt, Douglas M. Bennion, Colin Sumners; Cerebroprotective action of angiotensin peptides in stroke. Clin Sci (Lond) 1 February 2014; 126 (3): 195–205. doi: https://doi.org/10.1042/CS20130324
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