Cerebroprotective action of angiotensin peptides in stroke

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 nnultifactorial pathophysiology of stroke. Blocking the effects of Angll (angiotensin II) at AT(1)R (Angll type 1 receptor), through the use of commonly prescribed ACE (angiotensin-converting enzyme) inhibitors or AT(1)R blockers, has been shown to have therapeutic effects in both ischaemic and haemorrhagic stroke. In contrast with the deleterious actions of over activation of AT(1)R by Angll, stimulation of AT(2)Rs (Angll 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/Angll/AT(1)R 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 haennorrhagic 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.