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- Publisher Website: 10.1038/sj.bjp.0707387
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- PMID: 17618301
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Article: Therapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro
Title | Therapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro |
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Authors | |
Keywords | Coronary artery Nitric oxide synthase Raloxifene Vasoconstriction/dilation |
Issue Date | 2007 |
Publisher | John 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? |
Abstract | Background 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 Identifier | http://hdl.handle.net/10722/171360 |
ISSN | 2023 Impact Factor: 6.8 2023 SCImago Journal Rankings: 2.119 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Leung, FP | en_US |
dc.contributor.author | Yung, LM | en_US |
dc.contributor.author | Leung, HS | en_US |
dc.contributor.author | Au, CL | en_US |
dc.contributor.author | Yao, X | en_US |
dc.contributor.author | Vanhoutte, PM | en_US |
dc.contributor.author | Laher, I | en_US |
dc.contributor.author | Huang, Y | en_US |
dc.date.accessioned | 2012-10-30T06:13:36Z | - |
dc.date.available | 2012-10-30T06:13:36Z | - |
dc.date.issued | 2007 | en_US |
dc.identifier.citation | British Journal Of Pharmacology, 2007, v. 152 n. 2, p. 223-229 | en_US |
dc.identifier.issn | 0007-1188 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171360 | - |
dc.description.abstract | Background 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.language | eng | en_US |
dc.publisher | John Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1 | en_US |
dc.relation.ispartof | British Journal of Pharmacology | en_US |
dc.subject | Coronary artery | - |
dc.subject | Nitric oxide synthase | - |
dc.subject | Raloxifene | - |
dc.subject | Vasoconstriction/dilation | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Bradykinin - Pharmacology | en_US |
dc.subject.mesh | Coronary Vessels - Drug Effects - Physiology | en_US |
dc.subject.mesh | Estradiol - Analogs & Derivatives - Pharmacology | en_US |
dc.subject.mesh | Estrogen Antagonists - Pharmacology | en_US |
dc.subject.mesh | Muscle, Smooth, Vascular - Drug Effects - Physiology | en_US |
dc.subject.mesh | Nitric Oxide - Metabolism | en_US |
dc.subject.mesh | Nitric Oxide Synthase Type Iii - Metabolism | en_US |
dc.subject.mesh | Raloxifene - Pharmacology | en_US |
dc.subject.mesh | Swine | en_US |
dc.subject.mesh | Vasodilation - Drug Effects | en_US |
dc.subject.mesh | Vasodilator Agents - Pharmacology | en_US |
dc.title | Therapeutic concentrations of raloxifene augment nitric oxide-dependent coronary artery dilatation in vitro | en_US |
dc.type | Article | en_US |
dc.identifier.email | Vanhoutte, PM:vanhoutt@hku.hk | en_US |
dc.identifier.authority | Vanhoutte, PM=rp00238 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1038/sj.bjp.0707387 | en_US |
dc.identifier.pmid | 17618301 | - |
dc.identifier.scopus | eid_2-s2.0-34948886074 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-34948886074&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 152 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 223 | en_US |
dc.identifier.epage | 229 | en_US |
dc.identifier.isi | WOS:000249324800007 | - |
dc.publisher.place | United Kingdom | en_US |
dc.identifier.scopusauthorid | Leung, FP=8615375300 | en_US |
dc.identifier.scopusauthorid | Yung, LM=13807768200 | en_US |
dc.identifier.scopusauthorid | Leung, HS=13104316400 | en_US |
dc.identifier.scopusauthorid | Au, CL=7102805672 | en_US |
dc.identifier.scopusauthorid | Yao, X=7402529434 | en_US |
dc.identifier.scopusauthorid | Vanhoutte, PM=7202304247 | en_US |
dc.identifier.scopusauthorid | Laher, I=7005431686 | en_US |
dc.identifier.scopusauthorid | Huang, Y=7501573013 | en_US |
dc.identifier.issnl | 0007-1188 | - |