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Depressive Symptoms, Inflammation and Microvascular Dysfunction: Presence of a Gender Disparity
Author(s) -
Stanley Shyla C,
Butcher Joshua T,
Frisbee Stephanie J,
D'Audiffret Alexandre C,
Frisbee Jefferson C
Publication year - 2013
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.27.1_supplement.900.6
Subject(s) - dilator , endocrinology , medicine , sodium nitroprusside , inflammation , vasodilation , endothelial dysfunction , nitric oxide
Patients suffering from depressive symptoms have blunted vascular responses to dilator stimuli, with increasing evidence suggesting that this may be due to an inflammation/ROS‐induced loss in dilator metabolite bioavailability. We used the established unpredictable chronic mild stress (UCMS) model to simulate human clinical depression in mice. Endothelium‐dependent dilator responses in both conduit arteries (methacholine) and arterioles (acetylcholine) were attenuated by UCMS; more severely in males vs. females (responses to sodium nitroprusside were intact). Treatment with TEMPOL improved dilation in vessels from both genders. NOS inhibition had minimal impact on dilator responses in vessels of UCMS males, while reducing responses in females. Inhibition of COX blunted reactivity in UCMS males while exhibiting a muted effect in UCMS females. Impaired agonist‐induced vascular production of NO and PGI 2 in UCMS males versus females paralleled mechanical responses to NOS inhibition, but less well with COX inhibition (suggesting constrictor metabolites via COX may also contribute). The circulating levels of inflammatory markers MCP‐1 and TNF‐α were similar in both genders, despite the differences in dilator reactivity. These results suggest a greater susceptibility of males to UCMS‐induced production of ROS and inflammatory markers while protective mechanisms may blunt these effects in females.