File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Prostaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase

TitleProstaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase
Authors
Issue Date2007
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/
Citation
Hypertension, 2007, v. 50 n. 3, p. 525-530 How to Cite?
AbstractThe present experiments were designed to test the hypothesis that prostaglandin (PG) E2 causes vasodilatation through activation of endothelial NO synthase (eNOS). Aortic rings from mice with targeted deletion of eNOS and E-prostanoid (EP) receptors were used for contraction studies. Blood pressure changes in response to PGE2 were measured in conscious mice. Single doses of PGE2 caused concentration-dependent relaxations during contractions to phenylephrine (EC50=5*10 mol/L). Relaxation after PGE2 was absent in rings without endothelium and in rings from eNOS mice and was abolished by N-nitro-l-arginine methyl ester and the soluble guanylate cyclase inhibitor 1H-oxadiazolo-[4,3-a]quinoxalin-1-one. In PGE2-relaxed aortic rings, the cGMP content increased significantly. PGE2-induced relaxations were abolished by the EP4 receptor antagonist AE3-208 (10 mol/L) and mimicked by an EP4 agonist (AE1-329, 10 mol/L) in the presence of endothelium and eNOS only. Relaxations were attenuated significantly in rings from EP4 mice but normal in EP2. Inhibitors of the cAMP-protein kinase A pathway attenuated, whereas the inhibitor of protein phosphatase 1C, calyculin (10 mol/L), abolished the PGE2-mediated relaxation. In aortic rings, PGE2 dephosphorylated eNOS at Thr. Chronically catheterized eNOS mice were hypertensive (137±3.6 mm Hg, n=13, versus 101±3.9 mm Hg, n=9) and exhibited a lower sensitivity of blood pressure reduction in response to PGE2 compared with wild-type mice. There was no difference in the blood pressure response to nifedipine. These findings show that PGE2 elicits EP4 receptor-mediated, endothelium-dependent stimulation of eNOS activity by dephosphorylation at Thr resulting in guanylyl cyclase-dependent vasorelaxation and accumulation of cGMP in aortic rings. © 2007 American Heart Association, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/80272
ISSN
2015 Impact Factor: 6.294
2015 SCImago Journal Rankings: 3.702
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHristovska, AMen_HK
dc.contributor.authorRasmussen, LEen_HK
dc.contributor.authorHansen, PBLen_HK
dc.contributor.authorNielsen, SSen_HK
dc.contributor.authorNüsing, RMen_HK
dc.contributor.authorNarumiya, Sen_HK
dc.contributor.authorVanhoutte, Pen_HK
dc.contributor.authorSkøtt, Oen_HK
dc.contributor.authorJensen, BLen_HK
dc.date.accessioned2010-09-06T08:04:27Z-
dc.date.available2010-09-06T08:04:27Z-
dc.date.issued2007en_HK
dc.identifier.citationHypertension, 2007, v. 50 n. 3, p. 525-530en_HK
dc.identifier.issn0194-911Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/80272-
dc.description.abstractThe present experiments were designed to test the hypothesis that prostaglandin (PG) E2 causes vasodilatation through activation of endothelial NO synthase (eNOS). Aortic rings from mice with targeted deletion of eNOS and E-prostanoid (EP) receptors were used for contraction studies. Blood pressure changes in response to PGE2 were measured in conscious mice. Single doses of PGE2 caused concentration-dependent relaxations during contractions to phenylephrine (EC50=5*10 mol/L). Relaxation after PGE2 was absent in rings without endothelium and in rings from eNOS mice and was abolished by N-nitro-l-arginine methyl ester and the soluble guanylate cyclase inhibitor 1H-oxadiazolo-[4,3-a]quinoxalin-1-one. In PGE2-relaxed aortic rings, the cGMP content increased significantly. PGE2-induced relaxations were abolished by the EP4 receptor antagonist AE3-208 (10 mol/L) and mimicked by an EP4 agonist (AE1-329, 10 mol/L) in the presence of endothelium and eNOS only. Relaxations were attenuated significantly in rings from EP4 mice but normal in EP2. Inhibitors of the cAMP-protein kinase A pathway attenuated, whereas the inhibitor of protein phosphatase 1C, calyculin (10 mol/L), abolished the PGE2-mediated relaxation. In aortic rings, PGE2 dephosphorylated eNOS at Thr. Chronically catheterized eNOS mice were hypertensive (137±3.6 mm Hg, n=13, versus 101±3.9 mm Hg, n=9) and exhibited a lower sensitivity of blood pressure reduction in response to PGE2 compared with wild-type mice. There was no difference in the blood pressure response to nifedipine. These findings show that PGE2 elicits EP4 receptor-mediated, endothelium-dependent stimulation of eNOS activity by dephosphorylation at Thr resulting in guanylyl cyclase-dependent vasorelaxation and accumulation of cGMP in aortic rings. © 2007 American Heart Association, Inc.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://hyper.ahajournals.org/en_HK
dc.relation.ispartofHypertensionen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAorta - drug effects - physiologyen_HK
dc.subject.meshBlood Pressure - drug effectsen_HK
dc.subject.meshCyclic GMP - metabolismen_HK
dc.subject.meshDinoprostone - administration & dosage - pharmacologyen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshEndothelium, Vascular - physiologyen_HK
dc.subject.meshEnzyme Activation - physiologyen_HK
dc.subject.meshGuanylate Cyclase - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshNitric Oxide Synthase Type III - deficiency - metabolismen_HK
dc.subject.meshOsmolar Concentrationen_HK
dc.subject.meshPhosphorylation - drug effectsen_HK
dc.subject.meshReceptors, Prostaglandin E - physiologyen_HK
dc.subject.meshReceptors, Prostaglandin E, EP4 Subtypeen_HK
dc.subject.meshSignal Transduction - physiologyen_HK
dc.subject.meshVasodilation - physiologyen_HK
dc.titleProstaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-117X&volume=50&spage=525&epage=530&date=2007&atitle=Prostaglandin+E2+induces+vascular+relaxation+by+E-prostanoid+4+receptor-mediated+activation+of+endothelial+nitric+oxide+synthaseen_HK
dc.identifier.emailVanhoutte, P: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, P=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/HYPERTENSIONAHA.107.088948en_HK
dc.identifier.pmid17635857-
dc.identifier.scopuseid_2-s2.0-34548150722en_HK
dc.identifier.hkuros151152en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34548150722&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume50en_HK
dc.identifier.issue3en_HK
dc.identifier.spage525en_HK
dc.identifier.epage530en_HK
dc.identifier.isiWOS:000248945100017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHristovska, AM=19933493100en_HK
dc.identifier.scopusauthoridRasmussen, LE=7201874847en_HK
dc.identifier.scopusauthoridHansen, PBL=35472646600en_HK
dc.identifier.scopusauthoridNielsen, SS=35559406300en_HK
dc.identifier.scopusauthoridNüsing, RM=7003403318en_HK
dc.identifier.scopusauthoridNarumiya, S=16304844000en_HK
dc.identifier.scopusauthoridVanhoutte, P=7202304247en_HK
dc.identifier.scopusauthoridSkøtt, O=7005724990en_HK
dc.identifier.scopusauthoridJensen, BL=35502338900en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats