Sex differences and central protective effect of 17beta-estradiol in the development of aldosterone/NaCl-induced hypertension.
The present study tested the hypotheses that male and female rats respond differently to subcutaneous infusions of aldosterone (Aldo; 1.8 microg.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 (Delta25.4 +/- 2.4 mmHg) than in females (Delta7.1 +/- 2.2 mmHg). Gonadectomy augmented Aldo/NaCl-induced hypertension in females (Delta18.2 +/- 2.0 mmHg) but had no effect in males (Delta23.1 +/- 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 17beta-estradiol (E(2)) inhibited the Aldo/NaCl increase in BP (Delta10.5 +/- 0.8) compared with that in central vehicle plus systemic Aldo/NaCl (Delta26.1 +/- 2.5 mmHg) rats. Combined administration of E(2) and estrogen receptor antagonist ICI182780 (ICI) blocked the protective effect of E(2) (Delta23.2 +/- 2.4 mmHg). In intact females central, but not peripheral, infusions of ICI augmented the Aldo/NaCl (Delta20.4 +/- 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.
Xue
Baojian
B
Dept. of Psychology, Univ. of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA. Baojian-Xue@uiowa.edu
Badaue-Passos
Daniel
D
Guo
Fang
F
Gomez-Sanchez
Celso E
CE
Hay
Meredith
M
Johnson
Alan Kim
AK
D000284:Administration, Oral; D000450:Aldosterone / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D000077267:Fulvestrant; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D012737:Sex Factors; D012965:Sodium Chloride / Q000008:administration & dosage; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D004965:Estrogen Antagonists; D005730:Ganglionic Blockers; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D018738:Hexamethonium; D012965:Sodium Chloride; D000450:Aldosterone; D004958:Estradiol