Angiotensin II Type 2 Receptor: A Target for Protection Against Hypertension, Metabolic Dysfunction, and Organ...

The renin-angiotensin system is of vital significance not only in the maintenance of blood pressure but also because of its role in the pathophysiology of different organ systems in the body. Of the 2 Ang II (angiotensin II) receptors, the AT₁R (Ang II type 1 receptor) has been extensively studied for its role in mediating the classical functions of Ang II, including vasoconstriction, stimulation of renal tubular sodium reabsorption, hormonal secretion, cell proliferation, inflammation, and oxidative stress. The other receptor, AT₂R (Ang II type 2 receptor), is abundantly expressed in both immune and nonimmune cells in fetal tissue. However, its expression is increased under pathological conditions in adult tissues. The role of AT₂R in counteracting AT₁R function has been discussed in the past 2 decades. However, with the discovery of the nonpeptide agonist C21, the significance of AT₂R in various pathologies such as obesity, hypertension, and kidney diseases have been examined. This review focuses on the most recent findings on the beneficial effects of AT₂R by summarizing both gene knockout studies as well as pharmacological studies, specifically highlighting its importance in blood pressure regulation, obesity/metabolism, organ protection, and relevance in the treatment of coronavirus disease 2019 (COVID-19).