title: The effect of etanercept on aortic nitric oxide-dependent vasorelaxation in an unpredictable chronic, mild stress model of depression in rats.
abstract: Stress has been recognized as a risk factor for cardiovascular disease and depression, but the correlation is not well understood. However, inflammation is known to have a crucial role in both cardiovascular disease and depression. Tumor necrosis factor alpha (TNF-α) is a major cytokine for the activation of neuroendocrine, immune and behavioral responses. Therefore, we aimed to explore the effects of etanercept, an anti-TNF-α fusion protein, on endothelium-dependent vascular reactivity, blood pressure and endothelial nitric oxide synthase (eNOS) immunoreactivity in a model of unpredictable chronic mild stress (UCMS). Male rats were exposed to UCMS for 8 weeks, and etanercept (0.8 mg/kg, weekly) was administered during UCMS induction. The systolic blood pressure was recorded by the tail cuff method, and the relaxant responses of the aorta induced by carbachol, sodium nitroprusside (SNP) and papaverine were evaluated in an isolated organ bath system. UCMS rats exhibited an impaired carbachol-induced relaxant response compared to control rats, but there were no significant differences in the SNP- and papaverine-induced relaxant responses between the control and stressed rats. Etanercept treatment improved the carbachol-induced endothelium dependent relaxations observed in rats that experienced UCMS. No significant change in the systemic blood pressure was observed, but decreased expression of eNOS was detected in the UCMS group. Moreover, there were no significant changes in the etanercept treatment group compared to the control rats. Our results suggest that TNF-α could be a mediator of vascular dysfunction associated with UCMS, which leads to decreased expression of eNOS.
authors.affiliation: Department of Dermatology, Kocaeli University, Medical Faculty, 41380, Kocaeli, Turkey. dbayramgurler@yahoo.com
authors.forename: Dilek
authors.initials: D
authors.lastname: Bayramgurler
authors.forename: Ayse
authors.initials: A
authors.lastname: Karson
authors.forename: Yusufhan
authors.initials: Y
authors.lastname: Yazir
authors.forename: Ipek Komsuoglu
authors.initials: IK
authors.lastname: Celikyurt
authors.forename: Sema
authors.initials: S
authors.lastname: Kurnaz
authors.forename: Tijen
authors.initials: T
authors.lastname: Utkan
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure; D002217:Carbachol / Q000494:pharmacology; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D000068800:Etanercept; D007074:Immunoglobulin G / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002217:Carbachol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000068800:Etanercept