Hydrocortisone modulates the effect of estradiol on endothelial nitric oxide synthase expression in human endothelial cells

The interaction between hydrocortisone and estradiol on the regulation of e ndothelial nitric oxide synthase (eNOS) expression was investigated in huma n umbilical vein endothelial cells (HUVECs). Following incubation in medium containing dextran-coated-charcoal-stripped serum (DCC-stripped medium) fo r 4 days, incubation of HUVECs with 0.1 nM estradiol for 24 hr in the absen ce of hydrocortisone increased levels of eNOS mRNA measured by ribonuclease protection assay above control (0 nM estradiol). 2 RM hydrocortisone appli ed for 24 hr preceding and during estradiol application inhibited the estra diol-elicited increase in eNOS mRNA levels, reducing mRNA levels from 134% +/- 14% of control to 85% +/- 5% of control. Significant (ANOVA, p <0.01) r eductions of estradiol-mediated increases of mRNA levels occurred over a ra nge of hydrocortisone concentrations (10 nM, p <0.05; 2 muM, p <0.05; n=3-1 2). In the presence of 2 muM hydrocortisone, 10 nM estradiol significantly reduced eNOS mRNA levels to 59% +/- 3% of control. The ability of hydrocort isone to block or reverse the estradiol-mediated increase in eNOS mRNA leve ls may provide a link between elevated hydrocortisone levels and decreased NO production, potentially contributing to the development of hypertension and cardiovascular disease in vivo and antagonizing cardioprotective effect s of estrogens. (C) 2001 Elsevier Science Inc. All rights reserved.