We have recently shown that vasoactive peptides such as angiotensin II (Ang II) and endothelin-1 (ET-1) increased the expression of Gi proteins and proliferation of A10 vascular smooth muscle cells (VSMC) through MAP kinase / PI3 kinase pathways. The present study was undertaken to examine the implication of growth factor receptor activation in Ang II-induced enhanced expression of Gi proteins and proliferation of A10 VSMC and to further investigate the underlying mechanisms responsible for these increases. Cell proliferation was determined by [3H]thymidine incorporation, and the expression of Gi proteins and the phosphorylation of ERK1/2 and epidermal growth factor receptor (EGFR) was determined by Western blotting. Treatment of A10 VSMC with Ang II enhanced the expression of Gi proteins, which was attenuated by Ang II AT1 receptor antagonist but not by AT2 receptor antagonist. The inhibitor of EGFR also attenuated the enhanced expression of Gi proteins induced by Ang II to control levels. In addition, Ang II enhanced the phosphorylation of EGFR in A10 VSMC, and this was restored to control levels by the EGFR inhibitor and antioxidants. Furthermore, Ang II also augmented the proliferation and ERK1/2 phosphorylation of A10 VSMC, which were restored to control levels by the EGFR inhibitor. These data suggest that the Ang II-induced increase in oxidative stress transactivates EGFR, which through MAP kinase signaling may contribute to the enhanced expression of Gi proteins and thereby to the increased proliferation of A10 VSMC.
Deficiency of epidermal growth factor receptor prevents angiotensin II‐induced hypertrophy, but not inward remodeling, in cerebral arterioles
