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In this webinar, Dr. Teresa Milner presents research using a mouse model of accelerated ovarian failure to explore estrogen's role in menopausal hypertension, highlighting the therapeutic potential of estrogen receptor beta agonists during menopause transition.

This webinar focuses on understanding the role of estrogen in menopausal hypertension, a topic previously complicated by confounding factors such as aging and the use of preclinical models that fail to adequately replicate natural menopause. Researchers have utilized a mouse model of accelerated ovarian failure (AOF), induced by 4-vinylcyclohexene diepoxide (VCD), to better simulate early and late stages of human menopause. This model has been instrumental in isolating the effects of estrogen on neurogenic hypertension, particularly in the hypothalamic paraventricular nucleus (PVN), a crucial brain region for blood pressure regulation. The studies highlight that in the peri-AOF stage, hypertension is linked to a signaling pathway involving estrogen receptor beta (ERb) and the NMDA-type glutamate receptor in PVN neurons.

The findings reveal that cyclic administration of an ERb agonist can reverse hypertension susceptibility in peri-AOF mice, but not in male mice, indicating a specific therapeutic potential during menopause. This treatment suppresses NMDA receptor signaling in PVN neurons expressing ERb, supporting the existence of a therapeutic window for managing hypertension during the menopause transition. These results provide promising preclinical evidence for the use of ERb agonists as a treatment strategy for menopausal hypertension, underscoring the importance of the AOF model in advancing our understanding of estrogen’s role in this condition.

Key Topics Include:

• The accelerated ovarian failure (AOF) mouse model mimics the hormonal changes (especially estrogen) seen in human perimenopause and postmenopause


• Slow-pressor angiotensin (AngII) infusion results in hypertension in peri-AOF, post-AOF female mice and male mice but not young female mice


• Following hypertension, peri-AOF and post-AOF mice have distinct changes in the distribution of glutamatergic NMDA (GluN1) and AMPA (GluA1) receptors in estrogen receptor beta (ERb) containing paraventricular hypothalamic (PVN) neurons


• Hypertensive peri-AOF mice have heightened GluN1 signaling and reactive oxygen species (ROS) production in ERb-containing PVN dendrites


• Cyclic ERb agonist administration reduced hypertension in AngII-treated peri-AOF females, but not AngII-treated males, and suppressed NMDA receptor signaling in ERb-expressing PVN neurons