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Article: Therapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro

TitleTherapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro
Authors
Issue Date2007
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, 2007, v. 152 n. 2, p. 223-229 How to Cite?
AbstractBackground and purpose: Raloxifene improves cardiovascular function. This study examines the hypothesis that therapeutic concentrations of raloxifene augment endothelium-dependent relaxation via up-regulation of eNOS expression and activity in porcine coronary arteries. Experimental approach: Isometric tension was measured in rings from isolated arteries. Intracellular Ca 2+ concentrations ([Ca 2+] i) in arterial endothelial cells were detected by Ca 2+ fluorescence imaging. Phosphorylation of eNOS at Ser-1177 was assayed by Western blot analysis. Key results: In arterial rings pre-contracted with 9,11-dideoxy-11α,9α- epoxy-methano-prostaglandin F 2α (U46619), treatment with raloxifene (1-3 nM) augmented bradykinin- or substance P-induced relaxation and this effect was antagonized by ICI 182,780, an estrogen receptor antagonist. The enhanced relaxation was abolished in rings treated with inhibitors of nitric oxide/cyclic GMP-dependent dilation, N G-nitro-L-arginine methyl ester (L-NAME) plus 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). In contrast, effects of raloxifene were unaffected after inhibition of endothelium-derived hyperpolarizing factors by charybdotoxin plus apamin. Raloxifene (3 nM) did not influence endothelium-independent relaxation to sodium nitroprusside. 17β-Estradiol (3-10 nM) also enhanced bradykinin-induced relaxation, which was inhibited by ICI 182,780. Treatment with raloxifene (3 nM) did not affect bradykinin-stimulated rise in endothelial cell [Ca 2+] i. Raloxifene, 17β-estradiol, and bradykinin increased eNOS phosphorylation at Ser-1177 and ICI 182,780 prevented effects of raloxifene or 17β-estradiol but not that of bradykinin. Raloxifene had neither additive nor antagonistic effects on 17β-estradiol-induced eNOS phosphorylation. Conclusions and implications: Raloxifene in therapeutically relevant concentrations augmented endothelial function in porcine coronary arteries in vitro through ICI 182,780-sensitive mechanisms that were associated with increased phosphorylation of eNOS but independent of changes in endothelial cell [Ca 2+] i. © 2007 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/171360
ISSN
2015 Impact Factor: 5.259
2015 SCImago Journal Rankings: 2.368
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, FPen_US
dc.contributor.authorYung, LMen_US
dc.contributor.authorLeung, HSen_US
dc.contributor.authorAu, CLen_US
dc.contributor.authorYao, Xen_US
dc.contributor.authorVanhoutte, PMen_US
dc.contributor.authorLaher, Ien_US
dc.contributor.authorHuang, Yen_US
dc.date.accessioned2012-10-30T06:13:36Z-
dc.date.available2012-10-30T06:13:36Z-
dc.date.issued2007en_US
dc.identifier.citationBritish Journal Of Pharmacology, 2007, v. 152 n. 2, p. 223-229en_US
dc.identifier.issn0007-1188en_US
dc.identifier.urihttp://hdl.handle.net/10722/171360-
dc.description.abstractBackground and purpose: Raloxifene improves cardiovascular function. This study examines the hypothesis that therapeutic concentrations of raloxifene augment endothelium-dependent relaxation via up-regulation of eNOS expression and activity in porcine coronary arteries. Experimental approach: Isometric tension was measured in rings from isolated arteries. Intracellular Ca 2+ concentrations ([Ca 2+] i) in arterial endothelial cells were detected by Ca 2+ fluorescence imaging. Phosphorylation of eNOS at Ser-1177 was assayed by Western blot analysis. Key results: In arterial rings pre-contracted with 9,11-dideoxy-11α,9α- epoxy-methano-prostaglandin F 2α (U46619), treatment with raloxifene (1-3 nM) augmented bradykinin- or substance P-induced relaxation and this effect was antagonized by ICI 182,780, an estrogen receptor antagonist. The enhanced relaxation was abolished in rings treated with inhibitors of nitric oxide/cyclic GMP-dependent dilation, N G-nitro-L-arginine methyl ester (L-NAME) plus 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). In contrast, effects of raloxifene were unaffected after inhibition of endothelium-derived hyperpolarizing factors by charybdotoxin plus apamin. Raloxifene (3 nM) did not influence endothelium-independent relaxation to sodium nitroprusside. 17β-Estradiol (3-10 nM) also enhanced bradykinin-induced relaxation, which was inhibited by ICI 182,780. Treatment with raloxifene (3 nM) did not affect bradykinin-stimulated rise in endothelial cell [Ca 2+] i. Raloxifene, 17β-estradiol, and bradykinin increased eNOS phosphorylation at Ser-1177 and ICI 182,780 prevented effects of raloxifene or 17β-estradiol but not that of bradykinin. Raloxifene had neither additive nor antagonistic effects on 17β-estradiol-induced eNOS phosphorylation. Conclusions and implications: Raloxifene in therapeutically relevant concentrations augmented endothelial function in porcine coronary arteries in vitro through ICI 182,780-sensitive mechanisms that were associated with increased phosphorylation of eNOS but independent of changes in endothelial cell [Ca 2+] i. © 2007 Nature Publishing Group All rights reserved.en_US
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_US
dc.relation.ispartofBritish Journal of Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBradykinin - Pharmacologyen_US
dc.subject.meshCoronary Vessels - Drug Effects - Physiologyen_US
dc.subject.meshEstradiol - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshEstrogen Antagonists - Pharmacologyen_US
dc.subject.meshMuscle, Smooth, Vascular - Drug Effects - Physiologyen_US
dc.subject.meshNitric Oxide - Metabolismen_US
dc.subject.meshNitric Oxide Synthase Type Iii - Metabolismen_US
dc.subject.meshRaloxifene - Pharmacologyen_US
dc.subject.meshSwineen_US
dc.subject.meshVasodilation - Drug Effectsen_US
dc.subject.meshVasodilator Agents - Pharmacologyen_US
dc.titleTherapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitroen_US
dc.typeArticleen_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.bjp.0707387en_US
dc.identifier.pmid17618301-
dc.identifier.scopuseid_2-s2.0-34948886074en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34948886074&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume152en_US
dc.identifier.issue2en_US
dc.identifier.spage223en_US
dc.identifier.epage229en_US
dc.identifier.isiWOS:000249324800007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLeung, FP=8615375300en_US
dc.identifier.scopusauthoridYung, LM=13807768200en_US
dc.identifier.scopusauthoridLeung, HS=13104316400en_US
dc.identifier.scopusauthoridAu, CL=7102805672en_US
dc.identifier.scopusauthoridYao, X=7402529434en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.scopusauthoridLaher, I=7005431686en_US
dc.identifier.scopusauthoridHuang, Y=7501573013en_US

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