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Article: Angiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic mice

TitleAngiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic mice
Authors
Issue Date2010
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/ars
Citation
Antioxidants And Redox Signaling, 2010, v. 13 n. 6, p. 757-768 How to Cite?
AbstractThe mechanisms underlying the effect of the renin-angiotensin-aldosterone system (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely understood. This study explored a causal relationship between RAAS activation and oxidative stress involved in diabetes-associated endothelial dysfunction. Daily oral administration of valsartan or enalapril at 10mg/kg/day to db/db mice for 6 weeks reversed the blunted acetylcholine-induced endothelium-dependent dilatations, suppressed the upregulated expression of angiotensin II type 1 receptor (AT1R) and NAD(P)H oxidase subunits (p22phox and p47phox), and reduced reactive oxygen species (ROS) production. Acute exposure to AT1R blocker losartan restored the impaired endothelium-dependent dilatations in aortas of db/db mice and also in renal arteries of diabetic patients (fasting plasma glucose level ≥7.0 mmol/l). Similar observations were also made with apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE fluorescence revealed an overproduction of ROS in db/db aortas which was sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented the impairment of endothelium-dependent dilatations under hyperglycemic conditions that were accompanied by high ROS production. The present study has identified an initiative role of AT1R activation in mediating endothelial dysfunction of arteries from db/db mice and diabetic patients. © 2010 Mary Ann Liebert, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/125034
ISSN
2015 Impact Factor: 7.093
2015 SCImago Journal Rankings: 3.134
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilCUHK 4653/08M
HKU 2/07C
CUHK Focused Investment Scheme
CUHK Li Ka Shing Institute of Health Sciences
Funding Information:

This study was supported by Hong Kong Research Grant Council (CUHK 4653/08M and HKU 2/07C), CUHK Focused Investment Scheme, and CUHK Li Ka Shing Institute of Health Sciences.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWong, WTen_HK
dc.contributor.authorTian, XYen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorNg, CFen_HK
dc.contributor.authorLee, HKen_HK
dc.contributor.authorChen, ZYen_HK
dc.contributor.authorAu, CLen_HK
dc.contributor.authorYao, Xen_HK
dc.contributor.authorHuang, Yen_HK
dc.date.accessioned2010-10-31T11:07:46Z-
dc.date.available2010-10-31T11:07:46Z-
dc.date.issued2010en_HK
dc.identifier.citationAntioxidants And Redox Signaling, 2010, v. 13 n. 6, p. 757-768en_HK
dc.identifier.issn1523-0864en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125034-
dc.description.abstractThe mechanisms underlying the effect of the renin-angiotensin-aldosterone system (RAAS) inhibition on endothelial dysfunction in type 2 diabetes are incompletely understood. This study explored a causal relationship between RAAS activation and oxidative stress involved in diabetes-associated endothelial dysfunction. Daily oral administration of valsartan or enalapril at 10mg/kg/day to db/db mice for 6 weeks reversed the blunted acetylcholine-induced endothelium-dependent dilatations, suppressed the upregulated expression of angiotensin II type 1 receptor (AT1R) and NAD(P)H oxidase subunits (p22phox and p47phox), and reduced reactive oxygen species (ROS) production. Acute exposure to AT1R blocker losartan restored the impaired endothelium-dependent dilatations in aortas of db/db mice and also in renal arteries of diabetic patients (fasting plasma glucose level ≥7.0 mmol/l). Similar observations were also made with apocynin, diphenyliodonium, or tempol treatment in db/db mouse aortas. DHE fluorescence revealed an overproduction of ROS in db/db aortas which was sensitive to inhibition by losartan or ROS scavengers. Losartan also prevented the impairment of endothelium-dependent dilatations under hyperglycemic conditions that were accompanied by high ROS production. The present study has identified an initiative role of AT1R activation in mediating endothelial dysfunction of arteries from db/db mice and diabetic patients. © 2010 Mary Ann Liebert, Inc.en_HK
dc.languageengen_HK
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/arsen_HK
dc.relation.ispartofAntioxidants and Redox Signalingen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis is a copy of an article published in the [Antioxidants and Redox Signaling] © [2010] [copyright Mary Ann Liebert, Inc.]; [Antioxidants and Redox Signaling] is available online at: http://www.liebertonline.com.-
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAngiotensin II - biosynthesisen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshDiabetes Mellitus, Type 2 - metabolismen_HK
dc.subject.meshEndothelial Cells - metabolismen_HK
dc.subject.meshGlucose - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshOxidative Stressen_HK
dc.subject.meshReceptor, Angiotensin, Type 1 - metabolismen_HK
dc.subject.meshReceptor, Angiotensin, Type 2 - metabolismen_HK
dc.subject.meshRenin-Angiotensin Systemen_HK
dc.titleAngiotensin II type 1 receptor-dependent oxidative stress mediates endothelial dysfunction in type 2 diabetic miceen_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1089/ars.2009.2831en_HK
dc.identifier.pmid20136508-
dc.identifier.scopuseid_2-s2.0-77952668483en_HK
dc.identifier.hkuros175936en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77952668483&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume13en_HK
dc.identifier.issue6en_HK
dc.identifier.spage757en_HK
dc.identifier.epage768en_HK
dc.identifier.isiWOS:000280119800004-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular dysfunction in obesity and diabetes: from risk prediction to therapeutic intervention-
dc.identifier.scopusauthoridWong, WT=35932584500en_HK
dc.identifier.scopusauthoridTian, XY=35768379500en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridNg, CF=8519137200en_HK
dc.identifier.scopusauthoridLee, HK=7501482998en_HK
dc.identifier.scopusauthoridChen, ZY=7409487061en_HK
dc.identifier.scopusauthoridAu, CL=7102805672en_HK
dc.identifier.scopusauthoridYao, X=7402529434en_HK
dc.identifier.scopusauthoridHuang, Y=7501573013en_HK
dc.identifier.citeulike8430048-

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