It has been proposed that estrogen delays and or prevents the onset of hypertension and may function to keep women """"""""cardiovascularly younger"""""""" than men of the same age. Similar observations have been made in experimental hypertensive animals, however, the underlying mechanisms of estrogen's protective effects are incompletely understood. Given the importance of estrogen replacement therapy in women's health, it is clear that an understanding of the cellular mechanisms underlying estrogen's cardiovascular protective effects is critical for continuing development of clinical therapies for the treatment of hypertension in women. Angiotensin II (Ang II) is an important factor in some forms of both clinical and experimental hypertension. Chronic intravenous infusions of low levels of Ang II in experimental animals result in an increase in blood pressure that involves an increased neurogenic contribution to the maintenance of blood pressure which is prevented by prior lesioning of the area postrema (3,6,33,57,95). It is thought that circulating Ang II acts on area postrema neurons to maintain the hypertension. The proposed studies will test the general hypothesis that estrogen protects against the Ang II induced hypertension by inhibiting the actions of Ang II on area postrema neurons. To test this hypothesis and to characterize the effects of estrogen (17beta-estradiol) on area postrema neurons, Ang II induced increases in blood pressure and baroreflex modulation, this proposal will utilize whole-cell patch clamp recordings from isolated area postrema neurons, in vivo single unit recordings of area postrema neurons and hemodynamic measurements in conscious animals to address the following 4 major and distinct aims. 1) To evaluate area postrema membrane properties following exposure to 17beta-estradiol. 2) To determine the effects of acute and chronic 17beta-estradiol on area postrema calcium handling. 3) To determine the effect of 17beta-estradiol on activation of area postrema neurons. 4) To evaluate the effects of acute and chronic 17beta-estradiol on Ang II hypertension. Determination of the effects of estrogen on CNS mechanisms underlying Ang II dependent hypertension will have a significant impact on our understanding of the cardiovascular benefits of estrogen replacement therapy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL062261-04
Application #
6629012
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Velletri, Paul A
Project Start
2000-02-15
Project End
2004-11-30
Budget Start
2003-02-01
Budget End
2004-11-30
Support Year
4
Fiscal Year
2003
Total Cost
$292,283
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Organized Research Units
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Sandberg, Kathryn; Ji, Hong; Hay, Meredith (2015) Sex-specific immune modulation of primary hypertension. Cell Immunol 294:95-101
Schiller, Crystal Edler; O'Hara, Michael W; Rubinow, David R et al. (2013) Estradiol modulates anhedonia and behavioral despair in rats and negative affect in a subgroup of women at high risk for postpartum depression. Physiol Behav 119:137-44
Xue, Baojian; Beltz, Terry G; Yu, Yang et al. (2011) Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension. Am J Physiol Heart Circ Physiol 300:H555-64
Xue, Baojian; Badaue-Passos Jr, Daniel; Guo, Fang et al. (2009) Sex differences and central protective effect of 17beta-estradiol in the development of aldosterone/NaCl-induced hypertension. Am J Physiol Heart Circ Physiol 296:H1577-85
Xue, Baojian; Singh, Minati; Guo, Fang et al. (2009) Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide. Am J Physiol Heart Circ Physiol 297:H1638-46
Xue, Baojian; Zhao, Yuanzi; Johnson, Alan Kim et al. (2008) Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species. Am J Physiol Heart Circ Physiol 295:H1025-H1032
Xue, B; Johnson, A K; Hay, M (2007) Sex differences in angiotensin II- induced hypertension. Braz J Med Biol Res 40:727-34
Xue, Baojian; Pamidimukkala, Jaya; Lubahn, Dennis B et al. (2007) Estrogen receptor-alpha mediates estrogen protection from angiotensin II-induced hypertension in conscious female mice. Am J Physiol Heart Circ Physiol 292:H1770-6
Pamidimukkala, Jaya; Xue, Baojian; Newton, Leslie G et al. (2005) Estrogen receptor-alpha mediates estrogen facilitation of baroreflex heart rate responses in conscious mice. Am J Physiol Heart Circ Physiol 288:H1063-70
Xue, Baojian; Pamidimukkala, Jaya; Hay, Meredith (2005) Sex differences in the development of angiotensin II-induced hypertension in conscious mice. Am J Physiol Heart Circ Physiol 288:H2177-84

Showing the most recent 10 out of 16 publications