Estrogen receptor-α mediates estrogen protection from angiotensin II-induced hypertension in conscious female

It has been shown that the female sex hormones have a protective role in the development of angiotensin II ( ANG II)- induced hypertension. The present study tested the hypotheses that 1) the estrogen receptor-alpha ( ER alpha) is involved in the protective effects of estrogen against ANG II-induced hypertension and 2) central ERs are involved. Blood pressure ( BP) was measured in female mice with the use of telemetry implants. ANG II ( 800 ng . kg(-1) . min(-1)) was administered subcutaneously via an osmotic pump. Baseline BP in the intact, ovariectomized ( OVX) wild-type ( WT) and ER alpha knockout ( ER alpha KO) mice was similar; however, the increase in BP induced by ANG II was greater in OVX WT ( 23.0 +/- 1.0 mmHg) and ER alpha KO mice ( 23.8 +/- 2.5 mmHg) than in intact WT mice ( 10.1 +/- 4.5 mmHg). In OVX WT mice, central infusion of 17 beta-estradiol ( E-2; 30 ng . kg(-1) . day(-1)) attenuated the pressor effect of ANG II ( 7.0 +/- 0.4 mmHg), and this protective effect of E-2 was prevented by coadministration of ICI-182,780 ( ICI; 1.5 mu g . kg(-1) . day(-1), 18.8 +/- 1.5 mmHg), a nonselective ER antagonist. Furthermore, central, but not peripheral, infusions of ICI augmented the pressor effects of ANG II in intact WT mice ( 17.8 +/- 4.2 mmHg). In contrast, the pressor effect of ANG II was unchanged in either central E-2-treated OVX ER alpha KO mice ( 19.0 +/- 1.1 mmHg) or central ICI-treated intact ER alpha KO mice ( 19.6 +/- 1.6 mmHg). Lastly, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction in BP in OVX WT, central ER antagonist-treated intact WT, central E-2 + ICI-treated OVX WT, ER alpha KO, and central E-2- or ICI-treated ER alpha KO mice compared with that in intact WT mice given just ANG II. Together, these data indicate that ER alpha, especially central expression of the ER, mediates the protective effects of estrogen against ANG II-induced hypertension.