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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1577    most recent 01255.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xue, B. Articles by Johnson, A. K. Search for Related Content PubMed PubMed Citation Articles by Xue, B. Articles by Johnson, A. K.

Sex differences and central protective effect of 17β-estradiol in the development of aldosterone/NaCl-induced hypertension

Departments of ¹Psychology, ²Pharmacology, and ³Integrative Physiology and the ⁴Cardiovascular Center, University of Iowa, Iowa City, Iowa; ⁵Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, Jackson, Mississippi; and ⁶Department of Physiology, University of Arizona, Tucson, Arizona

Submitted 2 December 2008 ; accepted in final form 2 March 2009

The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (Aldo; 1.8 µg·kg^–1·h^–1, 1% NaCl to drink; 28 days) and that central estrogen plays a protective role against the development of hypertension. In rats with blood pressure (BP) and heart rate (HR) measured by Data Sciences International telemetry, chronic Aldo/NaCl treatment induced a greater increase in BP in males (25.4 ± 2.4 mmHg) than in females (7.1 ± 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (18.2 ± 2.0 mmHg) but had no effect in males (23.1 ± 2.9 mmHg). Immunohistochemistry for Fra-like activity was higher in the paraventricular nucleus of intact males, castrated males, and ovariectomized (OVX) females compared with intact females after 28 days of Aldo/NaCl treatment. In intact males, central 17β-estradiol (E₂) inhibited the Aldo/NaCl increase in BP (10.5 ± 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (26.1 ± 2.5 mmHg) rats. Combined administration of E₂ and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E₂ (23.2 ± 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (20.4 ± 1.8 mmHg) BP increase. Finally, ganglionic blockade after Aldo infusions resulted in a smaller reduction in BP in intact females (–23.9 ± 2.5 mmHg) and in central estrogen-treated males (–30.2 ± 1.0 mmHg) compared with other groups (intact males, –39.3 ± 3.4; castrated males, –41.8 ± 1.9; intact males with central E₂ + ICI, –42.3 ± 2.1; OVX females, –40.3 ± 3.3; and intact females with central ICI, –39.1 ± 1.3 mmHg). Chronic Aldo infusion produced increases in NaCl intake and decreases in HR that were both similar in all groups. Taken together, the results indicate that central estrogen plays a protective role in the development of Aldo/NaCl-induced hypertension and that this may result from reduced sympathetic outflow.

estrogen receptor; blood pressure; heart rate; sympathetic nervous system