Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory

Neurobiol Learn Mem. 2012 Jan;97(1):113-23. doi: 10.1016/j.nlm.2011.10.003. Epub 2011 Oct 31.


It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / genetics
  • Angiotensin I / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 2 Receptor Blockers / pharmacology
  • Animals
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Imidazoles / pharmacology
  • Losartan / pharmacology
  • Mice
  • Mice, Knockout
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Pyridines / pharmacology
  • Receptors, Angiotensin / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Recognition, Psychology / drug effects
  • Recognition, Psychology / physiology*


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin II Type 2 Receptor Blockers
  • Imidazoles
  • Peptide Fragments
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Pyridines
  • Receptors, Angiotensin
  • Receptors, G-Protein-Coupled
  • PD 123319
  • Angiotensin I
  • angiotensin I (1-7)
  • Losartan