Women are exposed to estrogen in several forms including oral contraceptive pills and hormone replacement therapy. Although estrogen was originally believed to be cardioprotective, lately, its beneficial effects are being questioned. Prolonged exposure to estrogenic preparations increased the risk for cardiovascular diseases, but the mechanisms are still unknown. The paraventricular nucleus (PVN) of the hypothalamus and rostral ventrolateral medulla (RVLM) of the brainstem are two important cardiovascular centers that are well known to be involved in the central control of blood pressure (BP) regulation. My dissertation focuses on understanding the central mechanisms resulting in chronic estrogen-induced hypertension in a rat model. In my studies, chronic estradiol exposure increased arterial pressure and heart rate in female SD rats. These hypertensive effects of chronic estrogen exposure were accompanied with increased superoxide production in the RVLM. Treatment with an antioxidant reversed estradiol-induced increase in superoxide production in the RVLM and BP. Our studies also provide evidence that chronic estradiol exposure activates the endothelin-1 (ET-1) system in both the RVLM and PVN and intracerebroventricular administration of an ET-1 receptor antagonist reduced estradiol-induced increase in BP. Taken together, these findings suggest that the cardiovascular effects of estradiol may be attributed to a central component involving oxidative stress and activation of the endothelin system.
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