THE ANGIOTENSIN TYPE-2 RECEPTOR MEDIATES RNA-SYNTHESIS IN A10 VASCULAR SMOOTH-MUSCLE CELLS

This study was designed to define more precisely the relationship betw een specific angiotensin receptors and the growth of vascular smooth m uscle cells in response to angiotensin II. These experiments employed quiescent A10 cells which were characterized as smooth muscle by the e xpression 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 mu M) stimulated a hypertrophic response as indicated by an increase in RNA synthesis an d protooncogene expression in the absence of DNA synthesis. This incre ase in RNA synthesis could be blocked by PD123319, an AT(2) antagonist , but not by losartan, an AT(1) antagonist. RT-PCR analysis demonstrat ed that quiescent A10 cells express only the AT(2), receptor while pro liferating A10 cells express the AT(1a) and AT(1b) receptors in additi on to the AT(2) receptor. In addition, induction of AT(2) receptor-med iated RNA synthesis was prevented by indomethacin, a cyclooxygenase in hibitor. These studies therefore support a direct connection between t he AT(2) receptor and smooth muscle growth that is mediated, in part, by prostaglandin synthesis. (C) 1996 Academic Press Limited