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Article: Secretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteries

TitleSecretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteries
Authors
KeywordsNitric oxide
Secretogranin ii
Issue Date2011
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 2011, v. 300 n. 4, p. H1159-H1165 How to Cite?
AbstractSecretoneurin enhances the adhesion and transendothelial migration properties of monocytes and is a part of the peptide family encoded by the secretogranin II gene. The expression of the secretogranin II gene is upregulated in senescent endothelium. The present study was designed to examine the effects of secretoneurin on endothelium-dependent responsiveness. Isometric tension was measured in rings (with or without endothelium) of porcine coronary arteries. Secretoneurin did not induce contraction of quiescent or contracted rings. In preparations contracted by U-46619, relaxation was observed with high concentrations of the peptide. This relaxation was endothelium dependent and reduced by the nitric oxide synthase inhibitor N ω-nitro-L-arginine methyl ester (l-NAME). It was abolished when the preparations were incubated with l-NAME in combination with the cyclooxygenase inhibitor indomethacin. The relaxation was not affected by the combination of 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-etheno-7H-dibenzo[b,m][1,5,12,16]tetraazacyclotricosine-5,13-diiumditrifluoroacetate hydrate (UCL 1684), which abrogates endothelium-dependent hyperpolarizations. These results indicate that secretoneurin acutely induces relaxation through the activation of endothelial nitric oxide synthase (eNOS) and cyclooxygenase, with nitric oxide playing the dominant role. Prolonged (24 h) incubation with physiological concentrations of secretoneurin enhanced the relaxations to bradykinin and to the calcium ionophore A-23187, but this difference was not observed in preparations incubated with l-NAME or the calmodulin antagonist calmidazolium. Under these conditions, the relaxation to sodium nitroprusside remained unchanged. Incubation with secretoneurin significantly augmented the expression of eNOS and calmodulin as well as the dimerization of eNOS in cultures of porcine coronary arterial endothelial cells. These observations suggest that secretoneurin not only acutely causes but also, upon prolonged exposure, enhances endothelium-dependent relaxations.© 2011 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/135342
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
Funding AgencyGrant Number
Ministry of Education, Science and Technology (South Korea)R31-20029
HKU777208M
Funding Information:

This research was supported by the University of Hong Kong, Research Grant Council of the Hong Kong Special Administrative Region Grant HKU777208M, and World Class University Program Grant R31-20029, funded by the Ministry of Education, Science and Technology (South Korea).

References

 

DC FieldValueLanguage
dc.contributor.authorChan, CKYen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2011-07-27T01:33:54Z-
dc.date.available2011-07-27T01:33:54Z-
dc.date.issued2011en_HK
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 2011, v. 300 n. 4, p. H1159-H1165en_HK
dc.identifier.issn0363-6135en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135342-
dc.description.abstractSecretoneurin enhances the adhesion and transendothelial migration properties of monocytes and is a part of the peptide family encoded by the secretogranin II gene. The expression of the secretogranin II gene is upregulated in senescent endothelium. The present study was designed to examine the effects of secretoneurin on endothelium-dependent responsiveness. Isometric tension was measured in rings (with or without endothelium) of porcine coronary arteries. Secretoneurin did not induce contraction of quiescent or contracted rings. In preparations contracted by U-46619, relaxation was observed with high concentrations of the peptide. This relaxation was endothelium dependent and reduced by the nitric oxide synthase inhibitor N ω-nitro-L-arginine methyl ester (l-NAME). It was abolished when the preparations were incubated with l-NAME in combination with the cyclooxygenase inhibitor indomethacin. The relaxation was not affected by the combination of 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-etheno-7H-dibenzo[b,m][1,5,12,16]tetraazacyclotricosine-5,13-diiumditrifluoroacetate hydrate (UCL 1684), which abrogates endothelium-dependent hyperpolarizations. These results indicate that secretoneurin acutely induces relaxation through the activation of endothelial nitric oxide synthase (eNOS) and cyclooxygenase, with nitric oxide playing the dominant role. Prolonged (24 h) incubation with physiological concentrations of secretoneurin enhanced the relaxations to bradykinin and to the calcium ionophore A-23187, but this difference was not observed in preparations incubated with l-NAME or the calmodulin antagonist calmidazolium. Under these conditions, the relaxation to sodium nitroprusside remained unchanged. Incubation with secretoneurin significantly augmented the expression of eNOS and calmodulin as well as the dimerization of eNOS in cultures of porcine coronary arterial endothelial cells. These observations suggest that secretoneurin not only acutely causes but also, upon prolonged exposure, enhances endothelium-dependent relaxations.© 2011 the American Physiological Society.en_HK
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_HK
dc.rightsAmerican Journal of Physiology: Heart and Circulatory Physiology . Copyright © American Physiological Society.-
dc.subjectNitric oxideen_HK
dc.subjectSecretogranin iien_HK
dc.subject.meshCoronary Vessels - drug effects-
dc.subject.meshEndothelium, Vascular - drug effects-
dc.subject.meshNeuropeptides - pharmacology-
dc.subject.meshVasodilation - drug effects-
dc.subject.meshSecretogranin II - pharmacology-
dc.titleSecretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteriesen_HK
dc.typeArticleen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpheart.00519.2010en_HK
dc.identifier.pmid21297022-
dc.identifier.scopuseid_2-s2.0-79955060175en_HK
dc.identifier.hkuros186063en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955060175&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume300en_HK
dc.identifier.issue4en_HK
dc.identifier.spageH1159en_HK
dc.identifier.epageH1165en_HK
dc.identifier.isiWOS:000288942300003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, CKY=35209921200en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK

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