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

Abstract

BackgroundHypertension is the leading cause of cardiovascular disease worldwide. The etiology of essential hypertension is unknown. Psychological stress contributes to development of hypertension in humans. Estrogen has been shown to prevent stress‐induced hypertension in rodents with unknown mechanisms. Amygdala neurons have been implicated in controlling blood pressure. Abundant estrogen receptors, including estrogen receptor‐α (ERα), are expressed in the medial amygdala (MeA). Thus, we hypothesize that ERα expressed by MeA neurons mediates the anti‐hypertensive effects of estrogen during stress.MethodsWe use the Cre‐LoxP system to remove ERα from specific MeA neurons in mice (ERαlox/lox/SIM1‐Cre). Female ERαlox/lox/SIM1‐Cre mice and controls (ERαlox/lox) were subjected to bilateral ovariectomy (OVX), given a vehicle (V) or 17‐β‐Estradiol pellet (E2), and inserted with telemetry probes on day one. After a seven‐day recovery, blood pressure was recorded for 3 hours to establish baseline and then mice were subjected to 1 hour stress restraint.ResultsERαlox/lox OVX + V mice showed increased mean arterial blood pressure (MAP) and systolic arterial blood pressure (SAP) in response to stress, whereas this stress‐induced hypertension was blunted in ERαlox/lox OVX + E mice. Interestingly, ERαlox/lox/SIM1‐Cre OVX + E and OVX + V group both showed increased MAP and SAP in response to stress.ConclusionsOur results suggest that ERα in the MeA is required to mediate estrogenic actions to prevent stress‐induced hypertension.