Abstract Body: Objective: We previously found that male (M), but not female (F), Sprague-Dawley (SD) rats develop age-dependent hypertension (HTN) that is associated with cognitive impairment. We hypothesized that ovariectomy (OVRX) at midlife, to model human menopause, would induce hypertension and cognitive impairment with age.

Methods: In M and F SD rats at 3-, 8-, and 16-months-old (MO), blood pressure (MAP; mmHg) and sympathetic tone to the vasculature (iv hexamethonium, PeakΔMAP; mmHg) was measured via femoral artery cannulation. Recognition memory was assessed using the novel object recognition task. Blood brain barrier (BBB) integrity in the PVN was assessed as FITC extravasation following carotid artery cannulation. In a separate group of female rats at 8 MO, sham procedure, OVRX, or OVRX with estradiol replacement for 8-months (s.c. estradiol valerate, 1.5 mg extended-release pellet) was performed and rats were aged to 16MO. At 16MO, the previously described procedures were carried out.

Results: M, but not F, SD rats develop age-dependent HTN and increased sympathoexcitation that is associated with recognition memory deficits and BBB disruption. Following OVRX, female rats develop age-dependent HTN that is associated with recognition memory deficits and BBB disruption. Replacement of estrogen with 17β-estradiol prevented the development of HTN, cognitive impairment, and BBB disruption.

Conclusions: In males, HTN induces BBB disruption and is associated with cognitive impairment. Our studies suggest midlife loss of estrogen likely contributes to the development of age-dependent HTN and cognitive impairment in females. We speculate estrogen supplementation may mitigate HTN-related changes in memory with age.