Estrogen replacement therapy significantly reduces the risk of cardiovascular disease in postmenopausal women without altering circulating angiotensin II or aldosterone. Although increasing evidence suggests estrogen decreases vascular angiotensin II receptor expression and attenuates vascular responsiveness to angiotensin II, the effect of estrogen on adrenal aldosterone responses to angiotensin II and the effect of estrogen on aldosterone actions have surprisingly not been studied.
Aim 1 of this proposal will use radioligand-binding and immunohistochemical techniques to determine if estradiol alters the expression and distribution of the AT1 and AT2 subtypes of angiotensin II receptors in the rat adrenal.
Aim 2 will determine the effect of estradiol on angiotensin II-induced aldosterone secretion in conscious, ovariectomized rats.
Aim 3 will use rndioligand-binding, immunohistochemical, and electromobility supershift assay techniques to determine the effect of estradiol on the expression and activity of aldosterone's receptor, the mineralocorticoid receptor, in the kidney, heart, and brain. The results of these studies will reveal the influence of estradiol on adrenal aldosterone responses and actions and provide further insight into the mechanisms contributing to the well-known cardiovascular benefits of estrogen replacement therapy.
