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Article: Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats

TitleOxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive rats
Authors
Issue Date2012
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/ars
Citation
Antioxidants & Redox Signaling, 2012, v. 16 n. 4, p. 363-373 How to Cite?
AbstractAbstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.
Persistent Identifierhttp://hdl.handle.net/10722/146896
ISSN
2015 Impact Factor: 7.093
2015 SCImago Journal Rankings: 3.134
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong General Research Fund465308
466110
465611
UGC2041450
National Basic Research Program of China2012CB517805
Chinese University of Hong Kong
National Institutes of HealthRC2HL103400
1U01HL100397
Funding Information:

This study was supported by Hong Kong General Research Fund (465308, 466110, and 465611), UGC Direct Grant (2041450), National Basic Research Program of China (2012CB517805), Focused Investment Scheme from the Chinese University of Hong Kong, and the National Institutes of Health (RC2HL103400, 1U01HL100397).

References

 

DC FieldValueLanguage
dc.contributor.authorTian, XYen_HK
dc.contributor.authorWong, WTen_HK
dc.contributor.authorLeung, FPen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorWang, YXen_HK
dc.contributor.authorLee, HKen_HK
dc.contributor.authorNg, CFen_HK
dc.contributor.authorChen, ZYen_HK
dc.contributor.authorYao, Xen_HK
dc.contributor.authorAu, CLen_HK
dc.contributor.authorLau, CWen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorCooke, JPen_HK
dc.contributor.authorHuang, Yen_HK
dc.date.accessioned2012-05-23T05:48:52Z-
dc.date.available2012-05-23T05:48:52Z-
dc.date.issued2012en_HK
dc.identifier.citationAntioxidants & Redox Signaling, 2012, v. 16 n. 4, p. 363-373en_HK
dc.identifier.issn1523-0864en_HK
dc.identifier.urihttp://hdl.handle.net/10722/146896-
dc.description.abstractAbstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2alpha) (PGF(2alpha)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2alpha) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2alpha). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2alpha) plays an important role in mediating endothelial dysfunction in RH. Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2alpha) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.en_HK
dc.languageengen_US
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/arsen_HK
dc.relation.ispartofAntioxidants & Redox Signalingen_HK
dc.rightsThis is a copy of an article published in the [Antioxidants & Redox Signaling] © [2012] [copyright Mary Ann Liebert, Inc.]; [Antioxidants & Redox Signaling} is available online at: http://www.liebertonline.com.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleOxidative stress-dependent cyclooxygenase-2-derived prostaglandin F2α impairs endothelial function in renovascular hypertensive ratsen_HK
dc.typeArticleen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1089/ars.2010.3874en_HK
dc.identifier.pmid21951274-
dc.identifier.scopuseid_2-s2.0-84855392271en_HK
dc.identifier.hkuros199785en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855392271&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume16en_HK
dc.identifier.issue4en_HK
dc.identifier.spage363en_HK
dc.identifier.epage373en_HK
dc.identifier.isiWOS:000298814600007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHuang, Y=34770945300en_HK
dc.identifier.scopusauthoridCooke, JP=7202378672en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridLau, CW=7401968520en_HK
dc.identifier.scopusauthoridAu, CL=7102805672en_HK
dc.identifier.scopusauthoridYao, X=7402529434en_HK
dc.identifier.scopusauthoridChen, ZY=49662782700en_HK
dc.identifier.scopusauthoridNg, CF=8519137200en_HK
dc.identifier.scopusauthoridLee, HK=35300029200en_HK
dc.identifier.scopusauthoridWang, YX=24475591300en_HK
dc.identifier.scopusauthoridZhang, Y=54882358300en_HK
dc.identifier.scopusauthoridLeung, FP=8615375300en_HK
dc.identifier.scopusauthoridWong, WT=35932584500en_HK
dc.identifier.scopusauthoridTian, XY=35768379500en_HK

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