Estradiol attenuates angiotensin-induced aldosterone secretion in ovariectomized rats

Estrogen replacement therapy significantly reduces the risk of cardiovascul ar disease in postmenopausal women. Previous studies indicate that estradio l (E-2) decreases angiotensin II (AT) receptor density in the adrenal and p ituitary in NaCl-loaded rats. We used an in vivo model that eliminates the potentially confounding influence of ACTH to determine whether the E-2-indu ced decrease in adrenal AT receptor expression affects aldosterone response s to angiotensin LI (Ang II). Female rats were ovariectomized, treated with oil (OVX) or E-2 (OVX+E-2; 10 mug, sc) for 14 days, and fed a NaCl-deficie nt diet for the last 7 days to maximize adrenal AT receptor expression and responsiveness. On days 12-14 rats were treated with dexamethasone (DEX; 25 mug, ip, every 12 h) to suppress plasma ACTH. On day 14 aldosterone secret ion was measured after a 30-min infusion of Ang LI (330 ng/min). Ang II inf usion increased the peak plasma aldosterone levels to a lesser degree in th e OVX+E-2 than in the OVX rats (OVX, 1870 +/- 290 pg/ml; OVX+E-2, 1010 +/- 86 pg/ml; P < 0.05). Ang II-induced ACTH and aldosterone secretion was also studied in rats that were not treated with DEX. In the absence of DEX, the peak plasma aldosterone response was also significantly decreased (OVX, 53 60 +/- 1200 pg/ml; OVX/E-2, 2960 +/- 570 pg/ml; P < 0.05). However, E-2 als o reduced the plasma ACTH response to Ang II (P < 0.05; OVX, 220 +/- 29 pg/ ml; OVX+E-2, 160 +/- 20 pg/ml), suggesting that reduced pituitary ACTH resp onsiveness to Ang LI contributes to the effect of E-2 on Ang II-induced ald osterone secretion. Adrenal AT(1) binding studies confirmed that E-2 signif icantly reduces adrenal AT(1) receptor expression in both the presence and absence of DEX in NaCl-deprived rats. These results indicate that E-2-induc ed decreases in pituitary and adrenal AT(1) receptor expression are associa ted with attenuated pituitary ACTH and adrenal aldosterone responses to Ang II and suggest that estrogen replacement therapy may modulate Ang II-stimu lated aldosterone secretion as part of its well known cardioprotective acti ons.