ESTROGEN RESPONSIVE NEURONS IN THE MEDIAL AMYGDALA PREVENT STRESS‐INDUCED HYPERTENSION

Abstract

Psychological stress contributes to the development of hypertension in humans and this effect is partially mediated through the medial amygdala (MeA). Estrogens attenuate stress‐induced neural activity in the MeA. Estrogen receptor‐α (ERα) is highly expressed in the MeA. Thus, we hypothesize that estrogens prevent stress‐induced hypertension partly through actions on ERα expressed by MeA neurons. We used DREADD technology to selectively activate SIM1 neurons in the MeA in conscious mice and tested effects of MeA SIM1 neural activity on blood pressure (BP). In addition, Cre‐LoxP system was used to remove ERα from SIM1 neurons in female mice; in parallel, we stereotaxically injected AAV‐Cre into the MeA of ERαlox/lox female mice to delete ERα from all MeA neurons. We tested effects of estrogen replacement (vs. estrogen depletion) on stress‐induced hypertension in these mutant mice. Finally, we examined expression of glutamate receptors in amygdala in C57Bl/6 female mice with estrogen depletion or supplement, at no stress and stress conditions. We showed that selective activation of SIM1 neurons in the MeA increased basal BP and potentiated hypertensive responses provoked by psychological stress (restraint) in conscious mice. While estrogen replacement prevented stress‐induced hypertension in wild type female mice, deletion of ERα from SIM1 neurons, or deletion of ERα from the MeA attenuated these anti‐hypertensive effects of estrogens during stress. We revealed that estrogens increased glutamatergic membrane receptors under basal and stress restrain. To close, the antihypertensive effects of estrogens are partly mediated through ERα in the MeA neurons.