Cognitive benefits of angiotensin IV and angiotensin-(1–7): A systematic review of experimental studies

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Objectives:To explore effects of the brain renin-angiotensin system (RAS) on cognition.Design:Systematic review of experimental (non-human) studies assessing cognitive effects of RAS peptides angiotensin-(3–8) [Ang IV] and angiotensin-(1–7) [Ang-(1–7)] and their receptors, the Ang IV receptor (AT4R) and the Mas receptor.Results:Of 450 articles identified, 32 met inclusion criteria. Seven of 11 studies of normal animals found Ang IV had beneficial effects on tests of passive or conditioned avoidance and object recognition. In models of cognitive deficit, eight of nine studies found Ang IV and its analogs (Nle1-Ang IV, dihexa, LVV-hemorphin-7) improved performance on spatial working memory and passive avoidance tasks. Two of three studies examining Ang-(1–7) found it benefited memory. Mas receptor removal was associated with reduced fear memory in one study.Conclusion:Studies of cognitive impairment show salutary effects of acute administration of Ang IV and its analogs, as well as AT4R activation. Brain RAS peptides appear most effective administered intracerebroventricularly, close to the time of learning acquisition or retention testing. Ang-(1–7) shows anti-dementia qualities.HIGHLIGHTSAng IV and Ang-(1–7) have shown neuroprotective in animal models of cerebral injury.Ang IV and its analogs are linked to improved cognition in models of dementia or cognitive deficit.Cognitive effects of Ang-(1–7) are less studied but data show it benefits spatial working memory.RAS peptides are most effective administered i.c.v., close to the time of learning or testing.Dihexa may be the most promising compound for future testing in humans.

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