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Article: Cyclooxygenase-2-derived prostaglandin F2α mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging

TitleCyclooxygenase-2-derived prostaglandin F2α mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging
Authors
Issue Date2009
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 2009, v. 104 n. 2, p. 228-235 How to Cite?
AbstractHypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca]i) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane-prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca]i. RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F2α and prostacyclin (PGI2) increased by ACh; only PGF2α caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF2α were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane-prostanoid receptor-mediated ACh- or PGF2α-induced contractions and COX-2-dependent release of PGF2α. The present study demonstrates that PGF2α, derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane-prostanoid receptor-mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca]i. The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans. © 2009 American Heart Association, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/171375
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, SLen_US
dc.contributor.authorLeung, FPen_US
dc.contributor.authorLau, CWen_US
dc.contributor.authorAu, CLen_US
dc.contributor.authorYung, LMen_US
dc.contributor.authorYao, Xen_US
dc.contributor.authorChen, ZYen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorGollasch, Men_US
dc.contributor.authorHuang, Yen_US
dc.date.accessioned2012-10-30T06:13:42Z-
dc.date.available2012-10-30T06:13:42Z-
dc.date.issued2009en_US
dc.identifier.citationCirculation Research, 2009, v. 104 n. 2, p. 228-235en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/171375-
dc.description.abstractHypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca]i) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane-prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca]i. RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F2α and prostacyclin (PGI2) increased by ACh; only PGF2α caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF2α were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane-prostanoid receptor-mediated ACh- or PGF2α-induced contractions and COX-2-dependent release of PGF2α. The present study demonstrates that PGF2α, derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane-prostanoid receptor-mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca]i. The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans. © 2009 American Heart Association, Inc.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_US
dc.relation.ispartofCirculation Researchen_US
dc.rightsCirculation Research. Copyright © Lippincott Williams & Wilkins.-
dc.subject.meshAcetylcholine - Pharmacologyen_US
dc.subject.meshAge Factorsen_US
dc.subject.meshAgeden_US
dc.subject.meshAging - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta - Drug Effects - Enzymologyen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshCyclooxygenase 2 - Metabolismen_US
dc.subject.meshDinoprost - Metabolismen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshReactive Oxygen Species - Metabolismen_US
dc.subject.meshReceptors, Thromboxane - Metabolismen_US
dc.subject.meshRenal Artery - Enzymologyen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshVasoconstriction - Drug Effectsen_US
dc.subject.meshVasoconstrictor Agents - Pharmacologyen_US
dc.titleCyclooxygenase-2-derived prostaglandin F2α mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during agingen_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1161/CIRCRESAHA.108.179770en_US
dc.identifier.pmid19096033-
dc.identifier.scopuseid_2-s2.0-59849107087en_US
dc.identifier.hkuros166665-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-59849107087&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume104en_US
dc.identifier.issue2en_US
dc.identifier.spage228en_US
dc.identifier.epage235en_US
dc.identifier.isiWOS:000262909500014-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWong, SL=26634414200en_US
dc.identifier.scopusauthoridLeung, FP=8615375300en_US
dc.identifier.scopusauthoridLau, CW=7401968520en_US
dc.identifier.scopusauthoridAu, CL=7102805672en_US
dc.identifier.scopusauthoridYung, LM=13807768200en_US
dc.identifier.scopusauthoridYao, X=7402529434en_US
dc.identifier.scopusauthoridChen, ZY=7409487061en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridGollasch, M=7003908655en_US
dc.identifier.scopusauthoridHuang, Y=7501573013en_US

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