title: Angiotensin II type 2 receptor agonists: where should they be applied?
abstract: BACKGROUND
  Angiotensin II, the active endproduct of the renin-angiotensin system (RAS), exerts its effects via angiotensin II type 1 and type 2 (AT(1), AT(2)) receptors. AT(1) 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 II-AT(1) receptor interaction. Yet RAS blockade is often accompanied by rises in angiotensin II, which may exert beneficial effects via AT(2) receptors.
  
  
  METHODS
  This review summarizes our current knowledge on AT(2) receptors, describing their location, function(s), endogenous agonist(s) and intracellular signaling cascades. It discusses the beneficial effects obtained with C21, a recently developed AT(2) receptor agonist. Important questions that are addressed are do these receptors truly antagonize AT(1) receptor-mediated effects? What about their role in the diseased state and their heterodimerization with other receptors?
  
  
  CONCLUSIONS
  The general view that AT(2) receptors exclusively exert beneficial effects has been challenged, and in pathological models, their function sometimes mimics that of AT(1) receptors, for example, inducing vasoconstriction and cardiac hypertrophy. Yet given its upregulation in various pathological conditions, the AT(2) receptor remains a promising target for treatment, allowing effects beyond blood pressure-lowering, for example, in stroke, aneurysm formation, inflammation and myocardial fibrosis.
authors.affiliation: Erasmus Medical Center, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Verdonk
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Joep H M
authors.initials: JH
authors.lastname: van Esch
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006801:Humans; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II