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Article: Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

TitleEndothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries
Authors
KeywordsSoluble guanylyl cyclase
Nitric oxide
Calcium sensitization
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. 301 n. 6, p. H2313-H2321 How to Cite?
AbstractThe present study investigated the mechanism underlying the transient potentiation of vasoconstriction by hypoxia in isolated porcine coronary arteries. Isometric tension was measured in rings with or without endothelium. Hypoxia (Po(2) <30 mmHg) caused a transient further increase in tension (hypoxic augmentation) in contracted (with U46619) preparations. The hypoxic response was endothelium dependent and abolished by inhibitors of nitric oxide synthase [N(omega)-nitro-L-arginine methyl ester (L-NAME)] or soluble guanylyl cyclase (ODQ and NS2028). The addition of DETA NONOate (nitric oxide donor) in the presence of L-NAME restored the hypoxic augmentation, suggesting the involvement of the nitric oxide pathway. However, the same was not observed after incubation with 8-bromo-cyclic GMP, atrial natriuretic peptide, or isoproterenol. Assay of the cyclic GMP content showed no change upon exposure to hypoxia in preparations with and without endothelium. Incubation with protein kinase G and protein kinase A inhibitors did not inhibit the hypoxic augmentation. Thus the hypoxic augmentation is dependent on nitric oxide and soluble guanylyl cyclase but independent of cyclic GMP. The hypoxic augmentation persisted in calcium-free buffer and in the presence of nifedipine, ruling out a role for extracellular calcium influx. Hypoxia did not alter the intracellular calcium concentration, as measured by confocal fluorescence microscopy. This observation and the findings that hypoxic augmentation is enhanced by thapsigargin (sarco/endoplasmic reticulum calcium ATPase inhibitor) and inhibited by HA1077 or Y27632 (Rho kinase inhibitors) demonstrate the involvement of calcium sensitization in the phenomenon.© 2011 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/149120
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant Council780410M
Research Centre of Heart, Brain, Hormone and Healthy Aging of the University of Hong Kong
World Class University ProgramR31-20029
Ministry of Education, Science and Technology, South Korea
Funding Information:

This study was supported by Hong Kong Research Grant Council Grant No. 780410M (University of Hong Kong); by Research Centre of Heart, Brain, Hormone and Healthy Aging of the University of Hong Kong; and by the 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.authorMak, Jen_HK
dc.contributor.authorGao, Yen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2012-06-22T06:24:15Z-
dc.date.available2012-06-22T06:24:15Z-
dc.date.issued2011en_HK
dc.identifier.citationAmerican Journal of Physiology: Heart and Circulatory Physiology, 2011, v. 301 n. 6, p. H2313-H2321en_HK
dc.identifier.issn0363-6135en_HK
dc.identifier.urihttp://hdl.handle.net/10722/149120-
dc.description.abstractThe present study investigated the mechanism underlying the transient potentiation of vasoconstriction by hypoxia in isolated porcine coronary arteries. Isometric tension was measured in rings with or without endothelium. Hypoxia (Po(2) <30 mmHg) caused a transient further increase in tension (hypoxic augmentation) in contracted (with U46619) preparations. The hypoxic response was endothelium dependent and abolished by inhibitors of nitric oxide synthase [N(omega)-nitro-L-arginine methyl ester (L-NAME)] or soluble guanylyl cyclase (ODQ and NS2028). The addition of DETA NONOate (nitric oxide donor) in the presence of L-NAME restored the hypoxic augmentation, suggesting the involvement of the nitric oxide pathway. However, the same was not observed after incubation with 8-bromo-cyclic GMP, atrial natriuretic peptide, or isoproterenol. Assay of the cyclic GMP content showed no change upon exposure to hypoxia in preparations with and without endothelium. Incubation with protein kinase G and protein kinase A inhibitors did not inhibit the hypoxic augmentation. Thus the hypoxic augmentation is dependent on nitric oxide and soluble guanylyl cyclase but independent of cyclic GMP. The hypoxic augmentation persisted in calcium-free buffer and in the presence of nifedipine, ruling out a role for extracellular calcium influx. Hypoxia did not alter the intracellular calcium concentration, as measured by confocal fluorescence microscopy. This observation and the findings that hypoxic augmentation is enhanced by thapsigargin (sarco/endoplasmic reticulum calcium ATPase inhibitor) and inhibited by HA1077 or Y27632 (Rho kinase inhibitors) demonstrate the involvement of calcium sensitization in the phenomenon.© 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.subjectSoluble guanylyl cyclaseen_HK
dc.subjectNitric oxideen_HK
dc.subjectCalcium sensitizationen_HK
dc.subject.meshAnoxia - metabolism - physiopathology-
dc.subject.meshCoronary Vessels - drug effects - metabolism - physiopathology-
dc.subject.meshCyclic GMP - metabolism-
dc.subject.meshEndothelium, Vascular - drug effects - metabolism - physiopathology-
dc.subject.meshNitric Oxide - metabolism-
dc.subject.meshVasoconstriction - drug effects-
dc.titleEndothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteriesen_HK
dc.typeArticleen_HK
dc.identifier.emailMak, J: judymak@hku.hken_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityMak, J=rp00352en_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpheart.00258.2011en_HK
dc.identifier.pmid21984543-
dc.identifier.scopuseid_2-s2.0-82855169297en_HK
dc.identifier.hkuros200002en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-82855169297&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume301en_HK
dc.identifier.issue6en_HK
dc.identifier.spageH2313en_HK
dc.identifier.epageH2321en_HK
dc.identifier.isiWOS:000298325200017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.scopusauthoridGao, Y=54794138100en_HK
dc.identifier.scopusauthoridMak, J=7103323094en_HK
dc.identifier.scopusauthoridChan, CKY=35209921200en_HK

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