Interleukin-1beta-induced nitric oxide production in rat aortic endothelial cells: Inhibition by estradiol in normal and high glucose cultures

Expression of inducible nitric oxide synthase (iNOS) and the resultant incr eased nitric oxide (NO) production are associated with septic shock, athero sclerosis, and cytokine-induced vascular injury. Estrogen is known to impac t vascular injury and vascular tone, in part through regulation of NO produ ction. In the current study, we examined the effect of physiological concen trations of estradiol on interleukin-1beta (IL-1 beta)-induced NO productio n in rat aortic endothelial cells (RAECs). 17 beta-estradiol significantly decreased IL-1 beta-induced iNOS protein levels and reduced NO production i n RAECs. High glucose (25 mM) elevated the increase in IL-1 beta induced iN OS protein and NO production. Nevertheless, estradiol still inhibited IL-1 beta-induced iNOS and NO production even in the presence of high glucose. T hese data suggest that estradiol may exert its beneficial effects in part b y inhibiting induction of endothelial iNOS, a possible mechanism for the pr otective effect of estradiol against diabetes-associated cardiovascular com plications.