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Article: Oxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic rats

TitleOxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic rats
Authors
KeywordsCOX
NADPH oxidase
Oxidative stress
Streptozotocin-induced diabetes
Thromboxane prostanoid receptor
Vascular smooth muscle
Issue Date2008
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
Citation
British Journal Of Pharmacology, 2008, v. 154 n. 3, p. 639-651 How to Cite?
AbstractBackground and purpose: To investigate the dysfunction of vascular smooth muscle in streptozotocin-induced diabetic rats. Experimental approach: Rings without endothelium of femoral arteries were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals was measured with 2′,7′-dichlorodihydrofluorescein diacetate using confocal microscopy. The protein expressions were measured by western blotting. Key results: The concentration-response curves to U46619 and phenylephrine, but not that to KCl, were shifted to the left, suggesting a hypersensitivity of cell membrane receptors in diabetes. Exogenous oxygen-derived free radicals induced greater vasoconstrictions in the femoral artery from diabetic rats. Chronic treatment with apocynin (inhibitor of NADPH oxidase) and acute exposure to MnTMPyP (SOD/catalase mimetic) normalized the response. The catalase activity and the total glutathione level were reduced in arteries from streptozotocin-treated rats, confirming a redox abnormality. The basal oxidative state was higher in arteries from streptozotocin-treated rats and reduced in arteries from apocynin- and streptozotocin-treated rats, suggesting that the functional changes in diabetes are due to a chronic increase in oxidative stress. In the arteries of streptozotocin-treated rats, inhibitors of COX-1 and/or COX-2 prevented the hypersensitivity and reduced the increase in oxidative stress caused by phenylephrine and U46619, suggesting that both isoforms contribute to the smooth muscle dysfunction. The expression of proteins for COX-1 and COX-2 was increased in arteries of streptozotocin-treated rats and reduced in preparations of apocynin- and streptozotocin-treated rats. Conclusions and implications: Chronic diabetes and the resulting increased oxidative stress activate the production of COX-derived vasoconstrictor prostanoids causing hypersensitivity of vascular smooth muscle. © 2008 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/80256
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorShi, Yen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-09-06T08:04:16Z-
dc.date.available2010-09-06T08:04:16Z-
dc.date.issued2008en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2008, v. 154 n. 3, p. 639-651en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/80256-
dc.description.abstractBackground and purpose: To investigate the dysfunction of vascular smooth muscle in streptozotocin-induced diabetic rats. Experimental approach: Rings without endothelium of femoral arteries were suspended in organ chambers for isometric tension recording. The production of oxygen-derived free radicals was measured with 2′,7′-dichlorodihydrofluorescein diacetate using confocal microscopy. The protein expressions were measured by western blotting. Key results: The concentration-response curves to U46619 and phenylephrine, but not that to KCl, were shifted to the left, suggesting a hypersensitivity of cell membrane receptors in diabetes. Exogenous oxygen-derived free radicals induced greater vasoconstrictions in the femoral artery from diabetic rats. Chronic treatment with apocynin (inhibitor of NADPH oxidase) and acute exposure to MnTMPyP (SOD/catalase mimetic) normalized the response. The catalase activity and the total glutathione level were reduced in arteries from streptozotocin-treated rats, confirming a redox abnormality. The basal oxidative state was higher in arteries from streptozotocin-treated rats and reduced in arteries from apocynin- and streptozotocin-treated rats, suggesting that the functional changes in diabetes are due to a chronic increase in oxidative stress. In the arteries of streptozotocin-treated rats, inhibitors of COX-1 and/or COX-2 prevented the hypersensitivity and reduced the increase in oxidative stress caused by phenylephrine and U46619, suggesting that both isoforms contribute to the smooth muscle dysfunction. The expression of proteins for COX-1 and COX-2 was increased in arteries of streptozotocin-treated rats and reduced in preparations of apocynin- and streptozotocin-treated rats. Conclusions and implications: Chronic diabetes and the resulting increased oxidative stress activate the production of COX-derived vasoconstrictor prostanoids causing hypersensitivity of vascular smooth muscle. © 2008 Nature Publishing Group All rights reserved.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1en_HK
dc.relation.ispartofBritish Journal of Pharmacologyen_HK
dc.subjectCOXen_HK
dc.subjectNADPH oxidaseen_HK
dc.subjectOxidative stressen_HK
dc.subjectStreptozotocin-induced diabetesen_HK
dc.subjectThromboxane prostanoid receptoren_HK
dc.subjectVascular smooth muscleen_HK
dc.titleOxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1188&volume=154&spage=639&epage=651&date=2008&atitle=Oxidative+stress+and+COX+cause+hyper-responsiveness+in+vascular+smooth+muscle+of+the+femoral+artery+from+diabetic+ratsen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/bjp.2008.110en_HK
dc.identifier.pmid18414395-
dc.identifier.scopuseid_2-s2.0-44349193950en_HK
dc.identifier.hkuros151891en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44349193950&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume154en_HK
dc.identifier.issue3en_HK
dc.identifier.spage639en_HK
dc.identifier.epage651en_HK
dc.identifier.isiWOS:000256133600014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridShi, Y=7404964959en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK

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