Angiotensin III activates ERK1/2 mitogen activated protein kinases and proliferation of rat vascular smooth muscle cells.

Abstract

The proliferative effects of angiotensin (Ang) II in vascular smooth muscle cells (VSMCs) through its ability to stimulate extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway have been established. The main goal of this study was to explore whether Ang III induces ERK1/2 MAPK and VSMC proliferation in cultured Wistar VSMCs. Further, the Ang III actions were compared to those observed in VSMCs derived from the spontaneously hypertensive rat (SHR). We hypothesized that in VSMCs Ang III will have similar actions as Ang II to induce ERK1/2 MAPK and cellular proliferation and this ability may be different in VSMCs isolated from Wistar versus SHR rats. Time and/or concentration-dependent effects of Ang III and Ang II were determined in VSMCs using western blot analysis and DNA incorporation assay. The results showed that ERK1/2 MAPK phosphorylation mediated by Ang II or Ang III were concentration- and time-dependent in Wistar VSMCs. Moreover, Ang III was less effective in mediating ERK1/2 phosphorylation in SHR VSMCs as compared to effects seen in Wistar rat VSMCs. Ang III induced ERK1/2 phosphorylation through the AT1 receptors activation. Ang II and Ang III induced VSMC DNA synthesis via the AT1 receptor in a concentration-dependent manner in Wistar VSMCs. Moreover, Ang III induced VSMC proliferation and significant differences existed in the peptide's proliferation effects in Wistar versus SHR VSMCs. These results indicate that Ang III stimulates ERK1/2 MAPK and DNA synthesis in VSMCs via AT1 receptors. However, its ability to stimulate these pathways is reduced in SHR VSMCs.