Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the α-, but not β-, Estrogen Receptor

Abstract

Although estradiol (E 2 ) has been recognized to exert several vasculoprotective effects in several species, its effects in mouse vasomotion are unknown, and consequently, so is the estrogen receptor subtype mediating these effects. We investigated the effect of E 2 (80 μg/kg/day for 15 days) on NO production in the thoracic aorta of ovariectomized C57Bl/6 mice compared with those given placebo. E 2 increased basal NO production. In contrast, the relaxation in response to ATP, to the calcium ionophore A23187, and to sodium nitroprusside was unaltered by E 2 , whereas acetylcholine-elicited relaxation was decreased. The abundance of NO synthase I, II, and III immunoreactive proteins (using Western blot) in thoracic aorta homogenates was unchanged by E 2 . To determine the estrogen receptor (ER) subtype involved in these effects, transgenic mice in which either the ERα or ERβ has been disrupted were ovariectomized and treated, or not, with E 2 . Basal NO production was increased and the sensitivity to acetylcholine decreased in ERβ knockout mice in response to E 2 , whereas this effect was abolished in ERα knockout mice. Finally, these effects of E 2 on vasomotion required long-term and/or in vivo exposure, as short-term incubation of aortic rings with 10 nmol/L E 2 in the isolated organ chamber did not elicit any vasoactive effects. In conclusion, this study demonstrates that ERα, but not ERβ, mediates the beneficial effect of E 2 on basal NO production.