17 beta-estradiol decreases nitric oxide synthase II synthesis in vascularsmooth muscle cells

Several studies have provided evidence fur a direct effect of 17 beta-estra diol on vessel wall via interaction with the constitutively expressed nitri c oxide synthase (NOS) by endothelium. The aim of the present study was to investigate the effect of 17 beta-estradiol on inducible NOS (NOS II) in pr imary culture of smooth muscle cells (SMC) fram rat aorta. We here prove th at 17 beta-estradiol decreases the content and activity of NOS II in SMC. T his effect appears to be the consequence of ER activation, because: 1) ER a lpha: and ER beta are expressed in rat aorta SMC grown in culture; 2) low c oncentrations of hormone modulate NOS II activity; 3) the specific ER alpha antagonist ICI182,780 completely blocks 17 beta-estradiol effect, On the o ther hand, progesterone is deprived of any effect on NOS II content or acti vity, proving the specificity of 17 beta-estradiol effect. In addition, we show that 17 beta-estradiol can counteract the increase in NOS II activity following cytokine treatment. The observation could indicate a novel mechan ism for the protective effects exerted by these hormones in cardiovascular diseases and atherosclerosis in particular.