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IL‐10 KO female mice infused with TNF‐α show impaired ACh induced relaxation as compared to IL‐10KO male mice
Author(s) -
Zemse Saiprasad M.,
Hilgers Rob H. P.,
Cleghorn Donald,
Chiao Chin Wei,
Brands Michael,
Webb R. Clinton
Publication year - 2008
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.22.1_supplement.1235.5
Subject(s) - sodium nitroprusside , myograph , endocrinology , endothelial dysfunction , medicine , phenylephrine , cytokine , endothelium , tumor necrosis factor alpha , acetylcholine , chemistry , nitric oxide , blood pressure
Background: TNF‐α is a pro‐inflammatory cytokine, and is an important mediator of maternal endothelial dysfunction. In this study, we tested whether IL‐10 improves TNF‐α induced endothelial dysfunction. Methods: C57BL6/IL‐10 KO female and male mice were treated with saline or TNF‐α (220ng/kg/min) for 14 days. Aortic rings were isolated and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5mN. Endothelium‐dependent relaxation was assessed by constructing cumulative concentration‐response curves to acetylcholine (ACh, 0.001–10 μmol/L) during phenylephrine PE, 10 μmol/L)‐induced contraction. Endothelium‐independent relaxations were assessed by the NO donor sodium nitroprusside (SNP). Results: IL‐10 KO female mice treated with TNF‐ α showed significant impairment in ACh induced relaxation as compared to C57BL6 female mice treated with TNF‐ α (Emax = 52 ± 3% versus 76 ± 5% respectively; P<0.05). IL‐10 KO male mice treated with TNF‐α showed no significant impairment in ACh induced relaxation as compared to C57BL6 male mice treated with TNF‐α(Emax = 57 ± 3% versus 66 ± 3% respectively; P<0.05). TNF‐α infusion had no effect on endothelium‐independent relaxations by SNP in all the groups. Conclusion: The anti‐inflammatory cytokine IL‐10 prevents impairment in endothelium‐dependent vasorelaxation in response to 14 days of TNF‐α infusion which is more in female mice but not male mice.