Abstract
Ang-(1–7) is an effector peptide of the renin–angiotensin system with several distinct actions that are likely mediated by a specific receptor. Regulatory effects of angiotensin (Ang) peptides, Ang-(1–7) and Ang II, on Ang receptor 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 cells 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 and SHR/Crl VSMC. Ang-(1–7) did not affect AT1 mRNA levels in Crl lines. In conclusion, Ang-(1–7) regulates the AT1 receptor either directly or indirectly in a strain-specific fashion. The Ang-(1–7) antagonist, A-779, blocks the actions of Ang-(1–7) only in VSMC from WKY/Akr rats, suggesting either that 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 receptor mediated. Further, we found differences between Akr cells and Crl cells that are consistent with their genetic heterogeneity.
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