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

Baojian Xue, Daniel Badaue-Passos, Fang Guo, Celso E. Gomez-Sanchez, Meredith Hay, Alan Kim Johnson

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54 Scopus citations


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 (Δ25.4 ± 2.4 mmHg) than in females (Δ7.1 ± 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (Δ18.2 ± 2.0 mmHg) but had no effect in males (Δ23.1 ± 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 (E 2) inhibited the Aldo/NaCl increase in BP (Δ10.5 ± 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (Δ26.1 ± 2.5 mmHg) rats. Combined administration of E2 and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E 2 (Δ23.2 ± 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (Δ20.4 ± 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.

Original languageEnglish (US)
Pages (from-to)H1577-H1585
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - May 2009


  • Blood pressure
  • Estrogen receptor
  • Heart rate
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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