The Angiotensin Type 2 Receptor Mediates RNA Synthesis in A10 Vascular Smooth Muscle Cells

This study was designed to define more precisely the relationship between specific angiotensin receptors and the growth of vascular smooth muscle cells in response to angiotensin II. These experiments employed quiescent A10 cells which were characterized as smooth muscle by the expression of specific contractile proteins. Cell growth was monitored by measuring the incorporation of metabolic precursors into RNA or DNA. The treatment of A10 cells with angiotensin II (1 μ ) stimulated a hypertrophic response as indicated by an increase in RNA synthesis and protooncogene expression in the absence of DNA synthesis. This increase in RNA synthesis could be blocked by PD123319, an AT2antagonist, but not by losartan, an AT1antagonist. RT-PCR analysis demonstrated that quiescent A10 cells express only the AT2receptor while proliferating A10 cells express the AT1aand AT1breceptors in addition to the AT2receptor. In addition, induction of AT2receptor-mediated RNA synthesis was prevented by indomethacin, a cyclooxygenase inhibitor. These studies therefore support a direct connection between the AT2receptor and smooth muscle growth that is mediated, in part, by prostaglandin synthesis.