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

PROTECTION FROM CHRONIC STRESS- AND DEPRESSIVE SYMPTOM-INDUCED VASCULAR ENDOTHELIAL DYSFUNCTION IN FEMALE RATS IS ABOLISHED BY PRE-EXISTING METABOLIC DISEASE.

J Kevin Shoemaker, Stan Hileman, Kent C Lemaster, Dwayne N Jackson, Steven D Brooks, Jefferson C Frisbee, Stephanie Frisbee, Samantha Milde, Paul D Chantler
While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and that for depressive symptoms; creating a combined condition of severely elevated cardiovascular disease risk. In this companion manuscript, we determine the impact of pre-existing metabolic disease on the relationship between chronic stress//depressive symptoms and vascular function, using the obese Zucker (OZR) and the unpredictable chronic mild stress UCMS models. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive symptoms on vascular function demonstrated in female lean Zucker rats (LZR). OZR, in general, exhibited an attenuated vasodilator reactivity under control conditions versus LZR. Although still impaired, female OZR demonstrated a superior conduit arterial and resistance arteriolar dilator reactivity under control conditions versus responses in either OZR males or ovariectomized (OVX)-females, largely a function of a better maintenance of vascular NO and PGI2bioavailability. However, combined imposition of metabolic syndrome and UCMS in OZR further impaired dilator reactivity in both vessel subtypes to a similarly severe extent, and abolished any protective effect in females versus males or OVX-females. The loss of vascular protection in female OZR with UCMS was reflected in vasodilator metabolite bioavailability, which closely matched that for both male and OVX-female OZR with UCMS. These results suggest that combined presentation of metabolic disease and depressive symptoms can overwhelm the vasoprotection identified in females, and that this may reflect a severe impairment to normal endothelial function.

Publisher URL: http://doi.org/10.1152/ajpheart.00648.2017

DOI: 10.1152/ajpheart.00648.2017

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