With respect to the potential use of an orally active APA inhibitor, a number of important issues remain including but not limited to: (1) the relative importance of AngIII and APA to blood pressure control comparing the brain and peripheral systems; (2) the influence of other peptidases upon the formation of angiotensin ligands; (3) the significance of the AT2 receptor subtype, and Ang(1-7) acting at the Mas receptor, in the control and treatment of essential hypertension. This evidence concerns the gene AGTR2 and essential hypertension.