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

Xue B, Badaue-Passos D Jr, Guo F, Gomez-Sanchez CE, Hay M, Johnson AK. Sex differences and central protective effect of 17 beta-estradiol in the development of aldosterone/NaCl-induced hypertension. Am J Physiol Heart Circ Physiol 296: H1577-H1585, 2009. First published March 6, 2009; doi:10.1152/ajpheart.01255.2008.-The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (Aldo; 1.8 mu g . 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 (Delta 25.4 +/- 2.4 mmHg) than in females (Delta 7.1 +/- 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (Delta 18.2 +/- 2.0 mmHg) but had no effect in males (Delta 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 17 beta-estradiol (E-2) inhibited the Aldo/NaCl increase in BP (Delta 10.5 +/- 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (Delta 26.1 +/- 2.5 mmHg) rats. Combined administration of E-2 and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E-2 (Delta 23.2 +/- 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (Delta 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 E-2 + 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.