The Role of Estradiol in the Behavioral and Cardiovascular Consequences of Social Stress in Females

Abstract

Repeated exposure to social stress results in the emergence of psychosocial disorders, which significantly increases the risk of cardiac morbidity. Depressed women are at a greater risk for the development of comorbid cardiovascular disease in comparison to depressed men. Furthermore, increased risk in females begins during puberty and ends following menopause, suggesting that ovarian hormones play a role. In this study, female rats were subjected to witnessing a social defeat encounter between an aggressive male resident and a male intruder. Female rats were implanted with a cardiovascular telemetry device and either ovariectomized (OVX) or sham OVX (intact). In study 1, stress‐induced cardiovascular consequences were measured in female intact vs OVX witness rats compared with controls. In study 2, all females were OVX and replaced with estradiol (E) or vehicle (V). Each witness was paired with an intruder, and placed behind a plexi‐glass partition in the resident cage for the 5 daily 15 min intruder defeat exposures. Cardiovascular telemetry from Study 1 indicated higher heart rate, blood pressure, and the occurrence of premature ventricular contractions (PVCs) and behavioral anhedonia during stress in intact female witnesses compared to OVX witness and controls. This suggests that ovarian hormones increase sensitivity to stress‐induced cardiac dysfunction and stress‐induced depressive‐like behavior. Study 2 identified a higher presence of the same cardiac dysfunction factors during stress in OVX+E witnesses versus OVX+V witnesses. This demonstrates that E plays a role in the increased vulnerability to stress‐induced cardiac and behavioral dysfunction. Ongoing studies are assessing the mechanism whereby, when combined with stress, E increases susceptibility to cardiac dysfunction through analyses of heart rate variability. These findings recapitulate the increased vulnerability to cardiovascular dysfunction in an intact, cycling female population that suffers from comorbid depressive disorders. These studies seek to identify why females who undergo stress are more vulnerable to the development of co‐morbid depression and cardiovascular disease, thereby allowing for the development of novel targeted therapeutics.Support or Funding InformationASPIRE18080‐16‐41861, 15SDG22430017, and P20GM103641