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Metabolic Syndrome Eliminates Vascular Protection Against Chronic Stress in Female Rats
Author(s) -
Stanley Shyla,
Brooks Steven,
Leon Camille,
d'Audiffret Alex,
Frisbee Jeff
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.789.4
Subject(s) - vasodilation , medicine , endocrinology , metabolic syndrome , endothelial dysfunction , vasoconstriction , nitric oxide , pathophysiology , chronic stress , obesity
Metabolic syndrome (MetSyn) is a risk factor for depression, yet the comorbid consequences of chronic stress/depression and MetSyn are not well understood. Using the Unpredictable Chronic Mild Stress (UCMS) model of depression, we previously characterized disparity in disease profile between male and female rats. Specifically, although females were more susceptible to UCMS induced depressive symptoms, they exhibited greater vasodilator responses versus males. However, protection from stress induced vasculopathy is not observed in UCMS females with underlying MetSyn. To interrogate potential mechanisms governing this loss of vascular protection, vascular reactivity was assessed in aortic rings and skeletal muscle arteries of lean and obese female Zucker rats (LZR‐F, OZR‐F) following 8 weeks of UCMS. Plasma levels of inflammatory markers were measured by electrochemiluminescence (Meso Scale Diagnostics). Impairment of the endothelial‐dependent vasodilator responses to pharmacological stimuli in both conduits and resistance arterioles was significantly greater in OZR‐F versus LZR‐F. OZR‐F also exhibited increased adrenergic sensitivity. Compared to LZRs, the dependence on nitric oxide as a vasodilator was significantly attenuated in OZR‐F, which exhibited greater dependence on PGI2 as a compensatory mechanism for reduced NO bioavailability. Plasma TNFα, IL‐6, and IL‐10 were elevated following UCMS, although significantly greater levels were observed in OZR‐F versus LZR‐F. These results suggest that MetSyn increases the inflammatory response to chronic stress, which may overwhelm the mechanisms imparting vascular protection in lean females. Comorbid MetSyn may alter the pathophysiology of stress‐induced vascular disease.