P70 Methylation of 2-hydroxyestradiol(2OHE; endogenous estradiol metabolite) to 2-methoxyestradiol (2MeOE; angiogenesis inhibitor)by COMT plays a key role in mediating the anti-mitogenic effects of 2OHE on vascular smooth muscle cell (SMC)growth. Catecholamines such as norepinephrine (NE) are also substrates for COMT and increased levels of NE are associated with vasoocclusive disorders. We hypothesize that increased endogenous synthesis/levels of NE under pathophysiological conditions may abrogate the vasoprotective effects of 2OHE by competing for COMT and inhibiting 2MeOE formation. To test this hypothesis we investigated the anti-mitogenic effects of .001-10μM 2OHE on 2.5% FCS-induced SMC growth (cell number, DNA synthesis [thymidine incorporation], collagen synthesis [proline incorporatio])in rat and human aortic SMCs in the presence and absence of NE (0.1-40μM). NE concentration-dependently abrogated the inhibitory effects of 2OHE on SMC growth and in the presence of 10μM NE the inhibitory curve of 2OHE on SMC growth was shifted to the right(P