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Article: Gap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive rats

TitleGap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive rats
Authors
Issue Date2008
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 2008, v. 327 n. 1, p. 148-153 How to Cite?
AbstractExperiments were designed to determine the effect of gap junction inhibitors on endothelium-dependent contractions. Isolated aortic rings of spontaneously hypertensive rats (SHR) were suspended in vitro for isometric force recording. The nonselective gap junction inhibitor, carbenoxolone, reduced endothelium-dependent contractions to acetylcholine and the calcium ionophore A23187 [5-methylamino-2-(2S,3R,5R,8S,9S)-3,5,9-trimethyl-2-(1-oxo-(1H-pyrrol-2- yl)propan-2-yl)-1,7-dioxaspiro-(5,5)undecan-8-yl)methyl)benzooxazole-4- carboxylic acid]. There was no or modest effect of the gap peptides 40Gap27, 37,43Gap27, or 43Gap26 when applied alone on endothelium-dependent contractions. However, the combined treatment with the three gap peptides significantly decreased endothelium-dependent contractions. The combined inhibition of the three connexins was not as effective as carbenoxolone, suggesting the involvement of other connexins in the process of endothelium-dependent contraction. The present study shows the involvement of gap junctions in endothelium-dependent contractions of the SHR aorta, presumably that of the combination of connexins 37, 40, and 43 rather than a single subtype of these proteins. Contractions of the vascular smooth muscle caused by 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619) and prostacyclin, but not to those of endoperoxides and phenylephrine, were reduced only minimally by carbenoxolone. Thus, if gap junction signaling is involved in the contraction of the vascular smooth muscle to thromboxane-prostanoid receptor agonists, their contribution is small. This suggests that the reduction of endothelium-dependent contractions by carbenoxolone and the gap peptides cannot be attributed to the homocellular gap junctions between vascular smooth muscle, but is more likely to involve the homocellular gap junctions between endothelial cells and/or myoendothelial gap junctions. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/59545
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
Funding AgencyGrant Number
Council of Hong Kong
University of Hong Kong
Funding Information:

This work was supported by a Competitive Earmarked Research Grant of the Research Grant Council of Hong Kong and by the Centre for Healthy Aging of the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, EHCen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-05-31T03:52:26Z-
dc.date.available2010-05-31T03:52:26Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2008, v. 327 n. 1, p. 148-153en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59545-
dc.description.abstractExperiments were designed to determine the effect of gap junction inhibitors on endothelium-dependent contractions. Isolated aortic rings of spontaneously hypertensive rats (SHR) were suspended in vitro for isometric force recording. The nonselective gap junction inhibitor, carbenoxolone, reduced endothelium-dependent contractions to acetylcholine and the calcium ionophore A23187 [5-methylamino-2-(2S,3R,5R,8S,9S)-3,5,9-trimethyl-2-(1-oxo-(1H-pyrrol-2- yl)propan-2-yl)-1,7-dioxaspiro-(5,5)undecan-8-yl)methyl)benzooxazole-4- carboxylic acid]. There was no or modest effect of the gap peptides 40Gap27, 37,43Gap27, or 43Gap26 when applied alone on endothelium-dependent contractions. However, the combined treatment with the three gap peptides significantly decreased endothelium-dependent contractions. The combined inhibition of the three connexins was not as effective as carbenoxolone, suggesting the involvement of other connexins in the process of endothelium-dependent contraction. The present study shows the involvement of gap junctions in endothelium-dependent contractions of the SHR aorta, presumably that of the combination of connexins 37, 40, and 43 rather than a single subtype of these proteins. Contractions of the vascular smooth muscle caused by 9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619) and prostacyclin, but not to those of endoperoxides and phenylephrine, were reduced only minimally by carbenoxolone. Thus, if gap junction signaling is involved in the contraction of the vascular smooth muscle to thromboxane-prostanoid receptor agonists, their contribution is small. This suggests that the reduction of endothelium-dependent contractions by carbenoxolone and the gap peptides cannot be attributed to the homocellular gap junctions between vascular smooth muscle, but is more likely to involve the homocellular gap junctions between endothelial cells and/or myoendothelial gap junctions. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_HK
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAorta, Thoracic - physiopathology-
dc.subject.meshCarbenoxolone - pharmacology-
dc.subject.meshEndothelium, Vascular - physiology-
dc.subject.meshHypertension - physiopathology-
dc.subject.meshVasoconstriction - drug effects-
dc.titleGap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3565&volume=327&issue=1&spage=148&epage=153&date=2008&atitle=Gap+junction+inhibitors+reduce+endothelium-dependent+contractions+in+the+aorta+of+sponteanously+hypertensive+rats-
dc.identifier.emailTang, EHC: evatang1@hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityTang, EHC=rp01382en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1124/jpet.108.140046en_HK
dc.identifier.pmid18632992-
dc.identifier.scopuseid_2-s2.0-52649097054en_HK
dc.identifier.hkuros167579en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-52649097054&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume327en_HK
dc.identifier.issue1en_HK
dc.identifier.spage148en_HK
dc.identifier.epage153en_HK
dc.identifier.isiWOS:000259323000017-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, EHC=9536518500en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK

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