Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings

Saiprasad M. Zemse, Rob H.P. Hilgers, R. Clinton Webb

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

ANG II stimulates the production of reactive oxygen species and activates proinflammatory cytokines leading to endothelial dysfunction. We hypothesized that the antiinflammatory cytokine IL-10 counteracts the impairment in endothelium-dependent ACh relaxation caused by ANG II. Aortic rings of C57BL/6 mice were incubated in DMEM in the presence of vehicle (deionized H 2O), ANG II (100 nmol/l), recombinant mouse IL-10 (300 ng/ml), or both ANG II and IL-10 for 22 h at 37̊C. After incubation, rings were mounted in a wire myograph to assess endothelium-dependent vasorelaxation to cumulative concentrations of ACh. Overnight exposure of aortic rings to ANG II resulted in blunted ACh-induced vasorelaxation compared with that shown in untreated rings (maximal response = 44 ± 3% vs. 64 ± 3%, respectively; P < 0.05). IL-10 treatment significantly restored this impairment in relaxation (63 ± 2%). In addition, the NADPH oxidase inhibitor apocynin restored the impairment in relaxation (maximal response = 76 ± 3%). Western blotting showed increased gp91phox expression (a subunit of NADPH oxidase) in response to ANG II. Vessels treated with a combination of ANG II and IL-10 showed decreased expression of gp91 phox. Immunohistochemical analysis showed increased gp91 phox expression in ANG II-treated vessels compared with those treated with combined ANG II and IL-10. We found that the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation in response to long-term incubation with ANG II via decreasing NADPH oxidase expression.

Original languageEnglish (US)
Pages (from-to)H3103-H3108
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • NADPH oxidase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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