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Insulin Resistance‐Independent Impairments to Arterial Endothelial Function with Depressive Symptoms in Mice
Author(s) -
Beckett Jordan A.L.,
James Milinda E.,
Stapleton Phoebe A.,
Goodwill Adam G.,
d'Audiffret Alexandre C.,
Frisbee Jefferson C.
Publication year - 2010
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.24.1_supplement.1044.3
Subject(s) - dilator , insulin resistance , medicine , endocrinology , inflammation , chronic stress , endothelial dysfunction , insulin
Previous studies have associated the presence of depressive symptoms with evolution of impaired vascular function. To determine contributing mechanisms, male mice were exposed to 8 weeks of unpredictable chronic mild stress (UCMS; e.g., wet bedding, predator sound/smell, random disruption of light/dark cycles), with indices of depressive behavior (coat status, grooming and mobility) becoming exacerbated vs. controls. In these studies, we consistently demonstrated an increased vascular oxidant stress, impaired vascular dilator reactivity, a loss in nitric oxide bioavailability and the development of H 2 O 2 as a compensatory dilator mechanism. However, we also determined that UCMS mice experience increased, but highly variable, insulin resistance and chronic inflammation. As such, while vascular impairments are consistent across animals, the predictive power of systemic markers of CVD risk, including fasting insulin, and plasma levels of TNF‐α and CRP were limited. Additionally, there was no clear correlation between insulin resistance severity and plasma levels of TNF‐α or IL‐1β in UCMS mice. As such, while there are trends between IR or inflammation and vascular dysfunction in UCMS mice, these are not robust relationships, suggesting that an unidentified mechanism outside of glycemic control or chronic inflammation may be a superior predictor of vascular outcomes in this murine model of depression.