Midlife ovariectomy evokes hypertension, neuroinflammation and cognitive impairment in female Sprague-Dawley Rats

Introduction: Hypertension (HTN) is the leading preventable cause of premature death worldwide and its prevalence increases with age. Significantly, hypertension is a key risk factor for the development of vascular cognitive impairment, which is the 2nd most common cause of dementia after Alzheimer’s Disease. Previously we have reported that intact male (M), but not intact female (F), Sprague-Dawley (SD) rats develop age-dependent HTN, hippocampal neuroinflammation, and cognitive impairment. Unlike humans, F SD rats do not experience menopause, which may protect them from these age-related adverse outcomes. Thus, we hypothesize that ovariectomy (OVRX) at midlife, to model the loss of the female sex steroids following menopause, will induce HTN, hippocampal neuroinflammation and impaired cognitive function in F SD rats. Methods: Groups of F SD rats aged 8 months old underwent a sham procedure or OVRX plus placebo or estradiol replacement (s.c. estradiol valerate, 1.5 mg extended-release pellet) were studied 6-weeks post OVRX. In all rats, mean arterial pressure (MAP) was measured via femoral artery cannulation, cognitive function was assessed by the novel object recognition test and hippocampal neuroinflammation was assessed by immunofluorescence for GFAP. Results: The efficacy of OVRX was validated by LC/MS assessment of plasma estradiol (Estradiol pg/mL: Sham OVRX: 18±3, OVRX CA3 GFAP % area Sham OVRX: 3.1±.0.4, OVRX Dentate Gyrus GFAP % area: Sham OVRX: 12.2±.1.4, OVRX & Placebo: 26.5±2.3, OVRX & 17βE2: 12.2±1.7, P< 0.05). Conclusions: Our studies suggest midlife loss of estrogen, as seen following menopause, contributes to the development of age-dependent HTN and HTN-driven cognitive impairment which involves hippocampal neuroinflammation. We speculate estrogen supplementation may mitigate age-related impairments in blood pressure regulation and cognitive function in postmenopausal women. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.