American Journal of Physiology - Heart and Circulatory Physiology
American Journal of Physiology - Heart and Circulatory Physiology
5 years ago

PROTECTION FROM VASCULAR DYSFUNCTION IN FEMALE RATS WITH CHRONIC STRESS AND DEPRESSIVE SYMPTOMS.

J Kevin Shoemaker, Stan Hileman, Kent C Lemaster, Dwayne N Jackson, Steven D Brooks, Jefferson C Frisbee, Stephanie Frisbee, Samantha Milde, Paul D Chantler
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 impacted. Higher resolution results from pharmacological and biochemical assays suggested that, in female rats with normal gonadal sex steroids, vasoactive metabolite profiles were better maintained than in male or OVX, despite increased depressive symptom severity (i.e., higher nitric oxide and PGI2, lower H2O2and TxA2bioavailability). These results suggest that female rats exhibit more severe depressive behaviors with UCMS, but are partially protected from the vasculopathy that afflicts males and females lacking normal sex hormone profiles. Determining how female sex hormones afford partial vascular protection from chronic stress and depression is a necessary step for addressing the burden that these conditions place on cardiovascular health.

Publisher URL: http://doi.org/10.1152/ajpheart.00647.2017

DOI: 10.1152/ajpheart.00647.2017

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