Angiotensin-(1-7) regulates the levels of angiotensin II receptor subtype AT1 mRNA differentially in a strain-specific fashion

Ang-(1-7) is an effector peptide of the renin-angiotensin system with sever al distinct actions that are likely mediated by a specific receptor. Regula tory effects of angiotensin (Ang) peptides, Ang-(1-7) and Ang II, on Ang re ceptor subtype 1 (AT1) mRNA expression were investigated in vascular smooth muscle cells (VSMC) from four University of Akron (Akr) rat strains (WKY, SHR and two backcross consomic lines SHR/y and SHR/a), and in SHR and WKY c ells from Charles River Laboratories (Crl). In WKY/Akr and SHR/Akr, Ang-(1- 7) treatment increased the levels of AT1 mRNA. This effect was inhibited by the specific Ang-(1-7) antagonist, A-779, in WKY/Akr but not SHR/Akr. Ang II had no effect in Akr cells, but it down-regulated AT1 mRNA in WKY/Crl an d SHR/Crl VSMC, Ang-(1-7) did not affect ATI mRNA levels in Crl lines. In c onclusion, Ang-(1-7) regulates the AT1 receptor either directly or indirect ly in a strain-specific fashion. The Ang-(1-7) antagonist, A-779, blocks th e actions of Ang-(1-7) only in VSMC from WKY/Akr rats, suggesting either th at the binding sites for Ang-(1-7) have different properties in SHR/Akr and WKY/Akr cell lines, or that some of the effects of Ang-(1-7) are not recep tor mediated. Further, we found differences between Akr cells and Crl cells that are consistent with their genetic heterogeneity. (C) 2000 Elsevier Sc ience B.V. All rights reserved.