The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The classic RAS can be defined as the ACE-Ang II-AT1R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1–7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, inhibition of cell growth, anti-thrombosis and anti-arrhythmogenic effects, natriuresis, diuresis, and oxidative stress. The Mas receptor is expressed in brain, testis, heart, and kidney, and is proven to be a Gq-coupled receptor that in early studies was suggested to be an angiotensin II (ANG II) receptor.