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Article: Rosuvastatin improves endothelial function in db/db mice: Role of angiotensin II type 1 receptors and oxidative stress

TitleRosuvastatin improves endothelial function in db/db mice: Role of angiotensin II type 1 receptors and oxidative stress
Authors
Keywordsdiabetes
endothelial function
oxidative stress
statin
vasodilatation
Issue Date2011
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, 2011, v. 164 n. 2 B, p. 598-606 How to Cite?
AbstractBACKGROUND AND PURPOSE HMG-CoA reductase inhibitors, statins, with lipid-reducing properties combat against atherosclerosis and diabetes. The favourable modulation of endothelial function may play a significant role in this effect. The present study aimed to investigate the cellular mechanisms responsible for the therapeutic benefits of rosuvastatin in ameliorating diabetes-associated endothelial dysfunction. EXPERIMENTAL APPROACH Twelve-week-old db/db diabetic mice were treated with rosuvastatin at 20 mg·kg -1·day -1 p.o.for 6 weeks. Isometric force was measured in isolated aortae and renal arteries. Protein expressions including angiotensin II type 1 receptor (AT 1R), NOX4, p22 phox, p67 phox, Rac-1, nitrotyrosine, phospho-ERK1/2 and phospho-p38 were determined by Western blotting, while reactive oxygen species (ROS) accumulation in the vascular wall was evaluated by dihydroethidium fluorescence and lucigenin assay. KEY RESULTS Rosuvastatin treatment of db/db mice reversed the impaired ACh-induced endothelium-dependent dilatations in both renal arteries and aortae and prevented the exaggerated contractions to angiotensin II and phenylephrine in db/db mouse renal arteries and aortae. Rosuvastatin reduced the elevated expressions of AT 1R, p22 phox and p67 phox, NOX4, Rac1, nitrotyrosine and phosphorylation of ERK1/2 and p38 MAPK and inhibited ROS production in aortae from db/db mice. CONCLUSIONS AND IMPLICATIONS The vasoprotective effects of rosuvastatin are attributed to an increase in NO bioavailability, which is probably achieved by its inhibition of ROS production from the AT 1R-NAD(P)H oxidase cascade. © 2011 The British Pharmacological Society.
Persistent Identifierhttp://hdl.handle.net/10722/139450
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Council of Hong KongHKU2/07C
HKU4/CRF10
CUHK Li Ka Shing Institute of Health Sciences
4653/08 M
466110
Funding Information:

This study was supported by Research Grants (4653/08 M, 466110) and Collaborative Research Fund (HKU2/07C and HKU4/CRF10) from the Research Council of Hong Kong, CUHK Focused Investment Scheme and CUHK Li Ka Shing Institute of Health Sciences.

References

 

DC FieldValueLanguage
dc.contributor.authorTian, XYen_HK
dc.contributor.authorWong, WTen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorChen, ZYen_HK
dc.contributor.authorLu, Yen_HK
dc.contributor.authorLiu, LMen_HK
dc.contributor.authorLee, VWen_HK
dc.contributor.authorLau, CWen_HK
dc.contributor.authorYao, Xen_HK
dc.contributor.authorHuang, Yen_HK
dc.date.accessioned2011-09-23T05:50:07Z-
dc.date.available2011-09-23T05:50:07Z-
dc.date.issued2011en_HK
dc.identifier.citationBritish Journal Of Pharmacology, 2011, v. 164 n. 2 B, p. 598-606en_HK
dc.identifier.issn0007-1188en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139450-
dc.description.abstractBACKGROUND AND PURPOSE HMG-CoA reductase inhibitors, statins, with lipid-reducing properties combat against atherosclerosis and diabetes. The favourable modulation of endothelial function may play a significant role in this effect. The present study aimed to investigate the cellular mechanisms responsible for the therapeutic benefits of rosuvastatin in ameliorating diabetes-associated endothelial dysfunction. EXPERIMENTAL APPROACH Twelve-week-old db/db diabetic mice were treated with rosuvastatin at 20 mg·kg -1·day -1 p.o.for 6 weeks. Isometric force was measured in isolated aortae and renal arteries. Protein expressions including angiotensin II type 1 receptor (AT 1R), NOX4, p22 phox, p67 phox, Rac-1, nitrotyrosine, phospho-ERK1/2 and phospho-p38 were determined by Western blotting, while reactive oxygen species (ROS) accumulation in the vascular wall was evaluated by dihydroethidium fluorescence and lucigenin assay. KEY RESULTS Rosuvastatin treatment of db/db mice reversed the impaired ACh-induced endothelium-dependent dilatations in both renal arteries and aortae and prevented the exaggerated contractions to angiotensin II and phenylephrine in db/db mouse renal arteries and aortae. Rosuvastatin reduced the elevated expressions of AT 1R, p22 phox and p67 phox, NOX4, Rac1, nitrotyrosine and phosphorylation of ERK1/2 and p38 MAPK and inhibited ROS production in aortae from db/db mice. CONCLUSIONS AND IMPLICATIONS The vasoprotective effects of rosuvastatin are attributed to an increase in NO bioavailability, which is probably achieved by its inhibition of ROS production from the AT 1R-NAD(P)H oxidase cascade. © 2011 The British Pharmacological Society.en_HK
dc.languageengen_US
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.rightsBritish Journal of Pharmacology. Copyright © John Wiley & Sons Ltd.-
dc.rightsSpecial Statement for Preprint only Before publication: 'This is a preprint of an article accepted for publication in [The Journal of Pathology] Copyright © ([year]) ([Pathological Society of Great Britain and Ireland])'. After publication: the preprint notice should be amended to follows: 'This is a preprint of an article published in [include the complete citation information for the final version of the Contribution as published in the print edition of the Journal]' For Cochrane Library/ Cochrane Database of Systematic Reviews, add statement & acknowledgement : ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 20XX, Issue X. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Please include reference to the Review and hyperlink to the original version using the following format e.g. Authors. Title of Review. Cochrane Database of Systematic Reviews 20XX, Issue #. Art. No.: CD00XXXX. DOI: 10.1002/14651858.CD00XXXX (insert persistent link to the article by using the URL: http://dx.doi.org/10.1002/14651858.CD00XXXX) (This statement should refer to the most recent issue of the Cochrane Database of Systematic Reviews in which the Review published.)-
dc.subjectdiabetesen_HK
dc.subjectendothelial functionen_HK
dc.subjectoxidative stressen_HK
dc.subjectstatinen_HK
dc.subjectvasodilatationen_HK
dc.subject.meshEndothelium, Vascular - drug effects - metabolism - physiology-
dc.subject.meshFluorobenzenes - pharmacology-
dc.subject.meshOxidative Stress - drug effects-
dc.subject.meshPyrimidines - pharmacology-
dc.subject.meshReceptor, Angiotensin, Type 1 - genetics - metabolism-
dc.titleRosuvastatin improves endothelial function in db/db mice: Role of angiotensin II type 1 receptors and oxidative stressen_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1476-5381.2011.01416.xen_HK
dc.identifier.pmid21486274-
dc.identifier.pmcidPMC3188899-
dc.identifier.scopuseid_2-s2.0-80052235716en_HK
dc.identifier.hkuros194036en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052235716&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume164en_HK
dc.identifier.issue2 Ben_HK
dc.identifier.spage598en_HK
dc.identifier.epage606en_HK
dc.identifier.eissn1476-5381-
dc.identifier.isiWOS:000294367700017-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTian, XY=35768379500en_HK
dc.identifier.scopusauthoridWong, WT=35932584500en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridChen, ZY=24831737500en_HK
dc.identifier.scopusauthoridLu, Y=50661717400en_HK
dc.identifier.scopusauthoridLiu, LM=50661588900en_HK
dc.identifier.scopusauthoridLee, VW=7402507380en_HK
dc.identifier.scopusauthoridLau, CW=7401968520en_HK
dc.identifier.scopusauthoridYao, X=7402529434en_HK
dc.identifier.scopusauthoridHuang, Y=49361498000en_HK

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