Background: Endogenous estradiol (E2) provides protective vascular effects that are lost after menopause. While menopausal E2 therapy conveys protection to healthy women after menopause, whether E2 is still protective in the face of postmenopausal cardiovascular disease is unknown. Hypothesis: We hypothesized that E2 would provide vascular benefits in normotensive but not hypertensive conditions. Methods: Female Long-Evans rats were ovariectomized at 46 weeks of age to mimic menopause and randomized to receive estradiol (E2) or vehicle (VEH) for 8 weeks. Animals were also randomized to remain normotensive (NT) or receive angiotensin II (Ang II; 700 ng/kg/min) to provoke hypertension (HT). Systolic blood pressure, body and heart weight, aortic E2 receptor expression, and aortic histology were assessed, and data was analyzed by two-way ANOVA. Results: There was a main effect of HT to increase systolic blood pressure (p< 0.001), heart weight (p< 0.001), and aortic wall area (p < 0.01), whereas E2 had no effect on these parameters. E2 reduced body weight (p = 0.001), increased uterine weight (p< 0.001), and decreased aortic mRNA for GPER (p=0.04), with no effect of HT. Conclusions: In this rat model of menopause, E2 did not provide vascular protection in either normotensive or hypertensive conditions. Future studies will assess whether the advanced age of this model may be a factor. These findings highlight the need to consider age and hypertensive environment when evaluating menopausal hormone therapy. Funding: AG071746 and the Summer Undergraduate Research Fellowship program, supported by the American Physiological Society. 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.
Cheeran et al. (Fri,) studied this question.