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Metabolic Syndrome and Chronic Stress: Convergent Pathologies Lead to Severe Vascular Impairment
Author(s) -
Brooks Steven,
Stanley S,
Leon C,
d'Audiffret A,
Frisbee J
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.789.6
Subject(s) - vasodilation , medicine , endocrinology , endothelial dysfunction , pathological , chronic stress , metabolic syndrome , cardiology , obesity
Chronic stress/depression and Metabolic Syndrome (MetSyn) are both risk factors for cardiovascular disease and impaired vascular function. Despite their prevalence, the pathological effects of comorbid MetSyn and chronic stress/depression are not well defined. The purpose of this study was to interrogate the behavioral and vascular effects of comorbid MetSyn and chronic stress. The Unpredictable Chronic Mild Stress (UCMS) protocol was imposed on lean and obese Zucker rats (LZR, OZR) of both sexes to induce depressive behaviors as assessed by coat score and sucrose splash test. Vasodilator/constrictor responses of endothelium and vascular smooth muscle, as well as myogenic reactivity were assessed in ex vivo aortic rings, middle cerebral arteries (MCA), and gracilis arterioles (GA). Plasma inflammatory markers were detected by electrochemiluminescence (Meso Scale Diagnostics). UCMS induced behavioral symptoms in all groups; male/female OZRs were the most severe. UCMS OZRs and LZRs all showed reduced endothelium‐dependent vasodilation in aortic rings, MCA, and GA, versus controls. LZR‐Females were less impaired than LZR‐Males, but UCMS OZRs of both sexes had severely blunted vasodilator responses (50‐60% of maximum). Compared to UCMS LZRs, UCMS OZRs had increased adrenergic tone as well as impaired myogenic reactivity in both the GA and MCA. Plasma levels of TNFα, IL‐6, IL‐10, and MCP‐1 were highest in UCMS OZRs. Chronic stress exacerbates behavioral symptoms and increases severity of vascular dysfunction in both large and small arteries in MetSyn animals, suggesting that the pathological effects of UCMS and MetSyn are synergistic. These findings may have implications for managing vascular health in patients with depression and comorbid CVD.