AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function

The renin-angiotensin system (RAS) is a coordinated hormonal cascade intimately involved in cardiovascular and renal control and blood pressure regulation. Angiotensin II (Ang II), the major RAS effector peptide, binds two distinct receptors, the angiotensin type-1 receptor (AT(1)R) and the angiotensin type-2 (AT(2)R) receptor. The vast majority of the physiological actions of Ang II, almost all of them detrimental, are mediated by AT(1)Rs. In contrast, AT(2)Rs negatively modulate the actions of AT(1)Rs under the majority of circumstances and generally possess beneficial effects. AT(2)Rs induce vasodilation in both resistance and capacitance vessels, mediating natriuresis directly and via interactions with dopamine D1 receptors in the renal proximal tubule. AT(2)Rs inhibit renin biosynthesis and secretion and protect the kidneys from inflammation and ischemic injury. Our understanding of the exact role of AT(2)Rs in physiology and pathophysiology continues to expand; the purpose of this review is to provide an up-to-date summary of the functional role of AT(2)Rs at the organ, tissue, cellular, and subcellular levels with emphasis on the vascular and renal actions that bear on blood pressure regulation and hypertension.