title: Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings.
abstract: ANG II stimulates the production of reactive oxygen species and activates proinflammatory cytokines leading to endothelial dysfunction. We hypothesized that the anti-inflammatory 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(2)O), ANG II (100 nmol/l), recombinant mouse IL-10 (300 ng/ml), or both ANG II and IL-10 for 22 h at 37 degrees C. 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 gp91(phox) 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.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA. szemse@students.mcg.edu
authors.forename: Saiprasad M
authors.initials: SM
authors.lastname: Zemse
authors.forename: Rob H P
authors.initials: RH
authors.lastname: Hilgers
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009213:Myography; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009924:Organ Culture Techniques; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D014665:Vasodilator Agents; D000804:Angiotensin II; D016753:Interleukin-10; C056165:acetovanillone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000109:Acetylcholine