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dc.contributor.authorLeo, C-H
dc.contributor.authorHart, JL
dc.contributor.authorWoodman, OL
dc.date.accessioned2020-12-17T03:34:25Z
dc.date.available2020-12-17T03:34:25Z
dc.date.issued2011-06-06
dc.identifierpii: PONE-D-11-06418
dc.identifier.citationLeo, C. -H., Hart, J. L. & Woodman, O. L. (2011). 3 ',4 '-Dihydroxyflavonol Reduces Superoxide and Improves Nitric Oxide Function in Diabetic Rat Mesenteric Arteries. PLOS ONE, 6 (6), https://doi.org/10.1371/journal.pone.0020813.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/254940
dc.description.abstractBACKGROUND: 3',4'-Dihydroxyflavonol (DiOHF) is an effective antioxidant that acutely preserves nitric oxide (NO) activity in the presence of elevated reactive oxygen species (ROS). We hypothesized that DiOHF treatment (7 days, 1 mg/kg per day s.c.) would improve relaxation in mesenteric arteries from diabetic rats where endothelial dysfunction is associated with elevated oxidant stress. METHODOLOGY/PRINCIPAL FINDINGS: In mesenteric arteries from diabetic rats there was an increase in ROS, measured by L-012 and 2',7'-dichlorodihydrofluorescein diacetate fluorescence. NADPH oxidase-derived superoxide levels, assayed by lucigenin chemiluminescence, were also significantly increased in diabetic mesenteric arteries (diabetes, 4892±946 counts/mg versus normal 2486±344 counts/mg, n = 7-10, p<0.01) associated with an increase in Nox2 expression but DiOHF (2094±300 counts/mg, n = 10, p<0.001) reversed that effect. Acetylcholine (ACh)-induced relaxation of mesenteric arteries was assessed using wire myography (pEC(50) = 7.94±0.13 n = 12). Diabetes significantly reduced the sensitivity to ACh and treatment with DiOHF prevented endothelial dysfunction (pEC(50), diabetic 6.86±0.12 versus diabetic+DiOHF, 7.49±0.13, n = 11, p<0.01). The contribution of NO versus endothelium-derived hyperpolarizing factor (EDHF) to ACh-induced relaxation was assessed by evaluating responses in the presence of TRAM-34+apamin+iberiotoxin or N-nitro-L-arginine+ODQ respectively. Diabetes impaired the contribution of both NO (maximum relaxation, R(max) diabetic 24±7 versus normal, 68±10, n = 9-10, p<0.01) and EDHF (pEC(50), diabetic 6.63±0.15 versus normal, 7.14±0.12, n = 10-11, p<0.01) to endothelium-dependent relaxation. DiOHF treatment did not significantly affect the EDHF contribution but enhanced NO-mediated relaxation (R(max) 69±6, n = 11, p<0.01). Western blotting demonstrated that diabetes also decreased expression and increased uncoupling of endothelial NO synthase (eNOS). Treatment of the diabetic rats with DiOHF significantly reduced vascular ROS and restored NO-mediated endothelium-dependent relaxation. Treatment of the diabetic rats with DiOHF also increased eNOS expression, both in total and as a dimer. CONCLUSIONS/SIGNIFICANCE: DiOHF improves NO activity in diabetes by reducing Nox2-dependent superoxide production and preventing eNOS uncoupling to improve endothelial function.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.title3 ',4 '-Dihydroxyflavonol Reduces Superoxide and Improves Nitric Oxide Function in Diabetic Rat Mesenteric Arteries
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0020813
melbourne.affiliation.departmentSchool of BioSciences
melbourne.source.titlePLoS One
melbourne.source.volume6
melbourne.source.issue6
dc.rights.licenseCC BY
melbourne.elementsid1230299
melbourne.contributor.authorLeo, Chen
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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