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Am J Physiol Heart Circ Physiol (December 1, 2006). doi:10.1152/ajpheart.01011.2005
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Submitted on September 22, 2005
Accepted on November 22, 2006

ESTROGEN RECEPTOR-{alpha} MEDIATES ESTROGEN PROTECTION FROM ANGIOTENSIN II-INDUCED HYPERTENSION IN CONSCIOUS FEMALE MICE

Baojian Xue1*, Jaya Pamidimukkala2, Dennis Lubahn3, and Meredith Hay4

1 Department of Psychology, University of Iowa, Iowa City, Iowa, United States
2 Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, United States
3 University of Missouri Center for Phytonutrient and Phytochemical Studies, University of Missouri-Columbia, Columbia, Missouri, United States
4 Department of Physiolgy & Biophysics, University of Iowa, Iowa City, Iowa, United States; Department of Psychology, University of Iowa, Iowa City, Iowa, United States

* To whom correspondence should be addressed. E-mail: baojian-xue{at}uiowa.edu.

It has been shown that the female sex hormones have a protective role in the development of Angiotensin II (ANG II) induced hypertension. The present study tested the hypotheses that 1) the estrogen receptor alpha (ER{alpha}) is involved in the protective effects of estrogen against ANG II induced hypertension and 2) that central ER{alpha} are involved. Blood pressure (BP) was measured in female mice with the use of telemetry implants. ANG II (800 ng/kg/min) was administered subcutaneously via an osmotic pump. Baseline BP in the intact, Ovariectomized (OVX) wild type (WT) and ER{alpha} KO mice were similar, however the increase in BP induced by ANG II was greater in OVX WT (23.0± 1.0 mmHg), ER{alpha} KO mice (23.8± 2.5 mmHg) than in intact WT mice (10.1± 4.5 mmHg). In OVX WT mice, central infusion of E2 (30 µg/kg/d) attenuated the pressor effect of ANG II (7.0± 0.4 mmHg), and this protective effect of E2 was prevented by co-administration of ICI182,780, a nonselective antagonist (ICI, 1.5 µg/kg/d, 18.8 ±1.5 mmHg). Furthermore, central (but not peripheral) infusions of ICI augmented the pressor effects of Ang II in intact WT mice (17.8 ±4.2 mmHg). In contrast, the pressor effect of ANG II was unchanged in either central E2 treated OVX ER{alpha}KO mice (19.0±1.1 mmHg) or central ICI treated intact ER{alpha}KO mice (19.6±1.6 mmHg). Lastly, ganglionic blockade on day 7 after Ang II infusions resulted in greater reduction in BP in OVX WT, central ER antagonist treated intact WT, central E2+ICI treated OVX WT, ER{alpha} KO and central E2 or ICI treated ER{alpha}KO mice as compared with intact WT mice given just ANG II. Together, these data indicate that ER{alpha} , especially central expression of the ER, mediates the protective effects of estrogen against Ang II induced hypertension.




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