Is there a functional cardiovascular role for AT2 receptors?

Abstract

AbstractThe presence of at least two major subtypes of mammalian angiotensin II (Ang II) receptors has been convincingly demonstrated with the use of selective non‐peptide receptor ligands. Subtype selective peptide ligands have also been identified. The role of AT1 receptors in mediating angiotensin II‐induced vascular smooth muscle contraction, aldosterone secretion and a host of other responses has been well documented. However, the role of the AT2 receptor has remained an enigma. The purpose of the studies presented here was to examine the potential role of AT2 receptors in cardiovascular responses in young animals in which the AT2 receptor predominates, and to examine Ang II responses in animals chronically treated with an AT2 receptor ligand. Ang II receptor binding assays and Ang II contractile responses were assessed in aortic tissue from neonatal rats; aortic binding was compared to liver binding in tissues from the same animals. Although AT2 receptors were expressed in neonatal aorta, the AT2 selective ligand PD 123319 had no effect on Ang II‐induced contractile responses in aortic rings from these neonatal rats. In adult rats acute administration of PD 123319 failed to inhibit Ang II‐induced increases in blood pressure; however, in rats treated for 10–12 days with PD 123319 Ang II‐induced pressor responses were inhibited roughly 40% compared to vehicle treated control rats. These data demonstrate that the AT2 receptor in the neonate may not play a role in Ang II induced vascular tone. However, there may be some resetting or interaction of Ang receptor subtypes in adults rats chronically exposed to an AT2 receptor ligand such that Ang‐II pressor responses are impaired. © 1993 Wiley‐Liss, Inc.