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

Neurosci Biobehav Rev. 2018 Sep;92:209-225. doi: 10.1016/j.neubiorev.2018.05.005. Epub 2018 May 4.


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.

Keywords: AT4R; Alzheimer’s disease; Angiotensin IV; Angiotensin-(1–7); Cognition; Renin-angiotensin system.

Publication types

  • Systematic Review

MeSH terms

  • Angiotensin I / therapeutic use*
  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / therapeutic use
  • Animals
  • Cognition Disorders / drug therapy*
  • Databases, Bibliographic / statistics & numerical data
  • Dementia / drug therapy*
  • Disease Models, Animal
  • Humans
  • Memory, Short-Term / drug effects
  • Peptide Fragments / therapeutic use*


  • Peptide Fragments
  • Angiotensin II
  • angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-
  • Angiotensin I
  • angiotensin I (1-7)