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Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the &agr;-, but not...
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Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the &agr;-, but not &bgr;-, Estrogen Receptor
作者:
B. Darblade,
C. Pendaries,
A. Krust,
S. Dupont,
M. Fouque,
J. Rami,
P. Chambon,
F. Bayard,
J. Arnal,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 90,
issue 4
页码: 413-419
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: nitric oxide synthase;endothelial cell;estrogens;estrogen receptor
数据来源: OVID
摘要:
Although estradiol (E2) 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 E2(80 &mgr;g/kg/day for 15 days) on NO production in the thoracic aorta of ovariectomized C57Bl/6 mice compared with those given placebo. E2increased basal NO production. In contrast, the relaxation in response to ATP, to the calcium ionophore A23187, and to sodium nitroprusside was unaltered by E2, 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 E2. To determine the estrogen receptor (ER) subtype involved in these effects, transgenic mice in which either the ER&agr; or ER&bgr; has been disrupted were ovariectomized and treated, or not, with E2. Basal NO production was increased and the sensitivity to acetylcholine decreased in ER&bgr; knockout mice in response to E2, whereas this effect was abolished in ER&agr; knockout mice. Finally, these effects of E2on vasomotion required long-term and/or in vivo exposure, as short-term incubation of aortic rings with 10 nmol/L E2in the isolated organ chamber did not elicit any vasoactive effects. In conclusion, this study demonstrates that ER&agr;, but not ER&bgr;, mediates the beneficial effect of E2on basal NO production.
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