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

Jean K Ho; Daniel A Nation

doi:10.1016/j.neubiorev.2018.05.005

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.

Authors

Jean K Ho¹, Daniel A Nation²

Affiliations

¹ Department of Psychology, University of Southern California, Los Angeles, CA, USA. Electronic address: jeanho@usc.edu.
² Department of Psychology, University of Southern California, Los Angeles, CA, USA. Electronic address: danation@usc.edu.

Abstract

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*

Substances

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

Grant support

R21 AG055034/AG/NIA NIH HHS/United States