Circulation Research. 2002;90:413-419
Published online before print January 17, 2002, doi: 10.1161/hh0402.105096
Published online before print January 17, 2002, doi: 10.1161/hh0402.105096
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© 2002 American Heart Association, Inc.
Molecular Medicine |
Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the 
-, but not ß-, Estrogen Receptor
From INSERM U397 et Laboratoire de Physiologie, Institut Louis Bugnard, CHU Rangueil, Toulouse (B.D., C.P., M.-J.F., J.R., F.B., J.-F.A.), and Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/College de France, Illkirch (A.K., S.D., P.C.), France.
Correspondence to J.-F. Arnal, INSERM U397, Institut Louis Bugnard, CHU Rangueil, 31054 Toulouse Cedex, France. E-mail arnal{at}rangueil.inserm.fr
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 µg/kg/day for 15 days) on NO production in the thoracic aorta of ovariectomized C57Bl/6 mice compared with those given placebo. E2 increased 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
or ERß has been disrupted were ovariectomized and treated, or not, with E2. Basal NO production was increased and the sensitivity to acetylcholine decreased in ERß knockout mice in response to E2, whereas this effect was abolished in ER knockout mice. Finally, these effects of E2 on vasomotion required long-term and/or in vivo exposure, as short-term incubation of aortic rings with 10 nmol/L E2 in the isolated organ chamber did not elicit any vasoactive effects. In conclusion, this study demonstrates that ER, but not ERß, mediates the beneficial effect of E2 on basal NO production.
Key Words: nitric oxide synthase • endothelial cell • estrogens • estrogen receptor
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