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Endothelial dysfunction in rat adjuvant-induced arthritis: Vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase

dc.contributor.authorHaruna, Yoshisukeen_US
dc.contributor.authorMorita, Yoshitakaen_US
dc.contributor.authorKomai, Norioen_US
dc.contributor.authorYada, Toyotakaen_US
dc.contributor.authorSakuta, Takeoen_US
dc.contributor.authorTomita, Naruyaen_US
dc.contributor.authorFox, David A.en_US
dc.contributor.authorKashihara, Naokien_US
dc.date.accessioned2007-07-11T18:12:51Z
dc.date.available2007-07-11T18:12:51Z
dc.date.issued2006-06en_US
dc.identifier.citationHaruna, Yoshisuke; Morita, Yoshitaka; Komai, Norio; Yada, Toyotaka; Sakuta, Takeo; Tomita, Naruya; Fox, David A.; Kashihara, Naoki (2006). "Endothelial dysfunction in rat adjuvant-induced arthritis: Vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthase." Arthritis & Rheumatism 54(6): 1847-1855. <http://hdl.handle.net/2027.42/55215>en_US
dc.identifier.issn0004-3591en_US
dc.identifier.issn1529-0131en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/55215
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16729278&dopt=citationen_US
dc.description.abstractObjective To investigate endothelial function and levels of vascular oxidative stress in rat adjuvant-induced arthritis (AIA), in view of mounting evidence for an association between rheumatoid arthritis (RA) and accelerated vascular disease. Methods Thoracic aortic rings were prepared from AIA and control rats. After preconstriction by norepinephrine, the vasodilatory response to acetylcholine was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine in AIA rat aortas were measured by Western blotting. Homogenates of the aortas were incubated with various substrates for superoxide-producing enzymes, and superoxide production was assessed by fluorogenic oxidation of dihydroethidium to ethidium. Expression of endothelial nitric oxide synthase (eNOS) in aortas was examined by real-time reverse transcriptase–polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin (BH 4 ), a critical eNOS cofactor, were determined by high-performance liquid chromatography. Results Endothelium-dependent relaxation of the aortic ring was significantly depressed in AIA rats compared with control rats. The amounts of HNE and nitrotyrosine were increased in AIA rat aortas, indicating overproduction of reactive oxygen species. Incubation of AIA rat aorta homogenates with NADH or L -arginine, a substrate of eNOS, resulted in a significant increase in superoxide production. Endothelial NOS was highly expressed in AIA rat aortas. Serum levels of BH 4 were significantly lower in AIA. Treatment of AIA with BH 4 reversed the endothelial dysfunction, suggesting that its deficiency may contribute to the uncoupling of eNOS. Conclusion Vascular dysfunction in RA can be partially modeled in animals. NAD(P)H oxidase and uncoupled eNOS are responsible for the increase in vascular oxidative stress, which is likely to be involved in the endothelial dysfunction in AIA.en_US
dc.format.extent146592 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
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dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.titleEndothelial dysfunction in rat adjuvant-induced arthritis: Vascular superoxide production by NAD(P)H oxidase and uncoupled endothelial nitric oxide synthaseen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelGeriatricsen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumUniversity of Michigan, Ann Arboren_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japan ; Dr. Morita is recipient of the 2005 Research Award from the Kawasaki Medical Foundation. ; Division of Nephrology and Rheumatology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.contributor.affiliationotherKawasaki Medical School, Kurashiki, Japanen_US
dc.identifier.pmid16729278en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/55215/1/21891_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/art.21891en_US
dc.identifier.sourceArthritis & Rheumatismen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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