Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin angiotensin system

Angiotensin(Ang)-(1-7) is now recognized as a biologically active component of renin-angiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the angiotensin-converting enzyme (ACE) homologue ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well-established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counter regulatory pathway within the RAS the actions of which are in opposition to the vasoconstrictor/proliferative arm of the RAS consisting of ACE, Ang II and AT1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT1 and AT2 receptors.