Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas

The renin-angiotensin system not only plays a critical role in blood pressure control but is also involved in learning and memory mechanisms. In addition to angiotensin (Ang) II, Ang-(1-7) may also have important biological activities in the brain. Here, we show for the first time that Ang-(1-7) enhances long-term potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1 receptor antagonists and selective Ang-(1-7) receptor antagonists demonstrate the existence of a distinct Ang-(1-7) receptor in the brain, the G-protein-coupled receptor Mas, encoded by the Mas protooncogene. We also show that the genetic deletion of this receptor abolishes the Ang-(1-7)-induced enhancement of LTP. Thus, we firstly demonstrate that Ang-(1-7) influences the induction of LTP in limbic structures implicating its distinct function in learning and memory mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1-7) in the brain.