Protection from vascular dysfunction in female rats with chronic stress and depressive symptoms

The increasing prevalence and severity of clinical depression is strongly correlated with vascular disease risk, creating a comorbid condition with poor outcomes, although demonstrating a sexual disparity where females are at lower risk than males for subsequent cardiovascular events. To determine potential mechanisms responsible for this protection against stress/depression-induced vasculopathy in females, we exposed male and female ({plus minus}ovariectomy) rats to the unpredictable chronic mild stress (UCMS) model for 8 weeks and determined depressive symptom severity, vascular reactivity in aortic rings (AR) and ex vivo middle cerebral arteries (MCA), and determined the profile of major metabolites regulating vascular tone. While all groups exhibited severe depressive behaviors from UCMS, levels in females were significantly worse than in males or OVX. In all groups, endothelium-dependent dilator reactivity was depressed in AR and MCA, although myogenic activation and vascular stiffness (MCA) were not...