Angiotensin II type 2 receptor agonists: Where should they be applied?

Introduction: Angiotensin II, the active endproduct of the reninangiotensin system (RAS), exerts its effects via angiotensin II type 1 and type 2 (AT1, AT2) receptors. AT1 receptors mediate all well-known effects of angiotensin II, ranging from vasoconstriction to tissue remodeling. Thus, to treat cardiovascular disease, RAS blockade aims at preventing angiotensin IIAT1 receptor interaction. Yet RAS blockade is often accompanied by rises in angiotensin II, which may exert beneficial effects via AT2 receptors. Areas covered: This review summarizes our current knowledge on AT2 receptors, describing their location, function(s), endogenous agonist(s) and intracellular signaling cascades. It discusses the beneficial effects obtained with C21, a recently developed AT2 receptor agonist. Important questions that are addressed are do these receptors truly antagonize AT1 receptor-mediated effects? What about their role in the diseased state and their heterodimerization with other receptors? Expert opinion: The general view that AT2 receptors exclusively exert beneficial effects has been challenged, and in pathological models, their function sometimes mimics that of AT1 receptors, for example, inducing vasoconstriction and cardiac hypertrophy. Yet given its upregulation in various pathological conditions, the AT2 receptor remains a promising target for treatment, allowing effects beyond blood pressure-lowering, for example, in stroke, aneurysm formation, inflammation and myocardial fibrosis.

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