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Article: Dexmedetomidine induces both relaxations and contractions, via different α2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the rat

TitleDexmedetomidine induces both relaxations and contractions, via different α2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the rat
Authors
Issue Date2010
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, 2010, v. 335 n. 3, p. 659-664 How to Cite?
AbstractDexmedetomidine is an α2-adrenoceptor agonist and anesthetic. The present study was designed to characterize the receptor subtypes and the downstream mechanisms of the vascular effects of dexmedetomidine in small (mesenteric artery) and large (aorta) arteries ex vivo. Isometric tension was measured in Sprague-Dawley rat mesenteric and aortic rings (with or without endothelium). To study relaxations, cumulative concentrations of dexmedetomidine, 5-bromo-N-(2-imidazolin-2-yl)-6-quinoxalinamine, (UK14304), or clonidine were added to rings contracted with 9,11-dideoxy-9α,11α- methanoepoxy prostaglandin F2α (U46619) in the presence or absence of indomethacin; Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME); 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5- dihydroimidazole maleate (BRL44408); 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl) ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride (ARC239); L-657,743, (2S-trans)-1,3,4,5′,6,6′,7,12b-octahydro-1′, 3′-dimethyl-spiro[2H-benzofuro[2,3-a]quinolizine-2,4′(1′H) -pyrimidin]-2′(3′H)-one hydrochloride hydrate (MK912); rauwolscine; prazosin; or pertussis toxin. To study contractions, dexmedetomidine was added to quiescent rings without endothelium or after incubation with L-NAME, rauwolscine, prazosin, indomethacin, or 3-[(6-amino-(4-chlorobenzensulfonyl)-2- methyl-5,6,7,8-tetrahydronaphth)-1-yl]propionic acid (S18886). Dexmedetomidine evoked relaxation at low concentrations (10 pM-30 nM) followed by contraction at higher concentrations (>30 nM) in the mesenteric artery. In the aorta, the relaxation was significantly smaller. The relaxation to dexmedetomidine depended on nitric oxide, endothelium, and Gi protein, and it was mediated by α2A/D-adrenoceptors and possibly α2B- adrenoceptors. The contraction was mediated mainly by α2B- and α1-adrenoceptors and involved the action of prostanoids. UK14304 and clonidine induced greater and smaller relaxations, respectively, than dexmedetomidine. In conclusion, depending on the concentration used and the presence of functional endothelium, dexmedetomidine may evoke both relaxation and contraction in isolated arteries. The vascular effects also vary depending on the blood vessel studied. Its vascular effect is different from that of clonidine and UK14304. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/135343
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 773509M
University of Hong Kong200710159019
Funding Information:

This work was supported in part by the general research fund of the Research Grants Council of Hong Kong [Grant HKU 773509M] and a University of Hong Kong Seed Funding for Basic Research Grant [Grant 200710159019] and partly by departmental funds.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWong, ESWen_HK
dc.contributor.authorMan, RYKen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorNg, KFJen_HK
dc.date.accessioned2011-07-27T01:33:55Z-
dc.date.available2011-07-27T01:33:55Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2010, v. 335 n. 3, p. 659-664en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135343-
dc.description.abstractDexmedetomidine is an α2-adrenoceptor agonist and anesthetic. The present study was designed to characterize the receptor subtypes and the downstream mechanisms of the vascular effects of dexmedetomidine in small (mesenteric artery) and large (aorta) arteries ex vivo. Isometric tension was measured in Sprague-Dawley rat mesenteric and aortic rings (with or without endothelium). To study relaxations, cumulative concentrations of dexmedetomidine, 5-bromo-N-(2-imidazolin-2-yl)-6-quinoxalinamine, (UK14304), or clonidine were added to rings contracted with 9,11-dideoxy-9α,11α- methanoepoxy prostaglandin F2α (U46619) in the presence or absence of indomethacin; Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME); 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5- dihydroimidazole maleate (BRL44408); 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl) ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride (ARC239); L-657,743, (2S-trans)-1,3,4,5′,6,6′,7,12b-octahydro-1′, 3′-dimethyl-spiro[2H-benzofuro[2,3-a]quinolizine-2,4′(1′H) -pyrimidin]-2′(3′H)-one hydrochloride hydrate (MK912); rauwolscine; prazosin; or pertussis toxin. To study contractions, dexmedetomidine was added to quiescent rings without endothelium or after incubation with L-NAME, rauwolscine, prazosin, indomethacin, or 3-[(6-amino-(4-chlorobenzensulfonyl)-2- methyl-5,6,7,8-tetrahydronaphth)-1-yl]propionic acid (S18886). Dexmedetomidine evoked relaxation at low concentrations (10 pM-30 nM) followed by contraction at higher concentrations (>30 nM) in the mesenteric artery. In the aorta, the relaxation was significantly smaller. The relaxation to dexmedetomidine depended on nitric oxide, endothelium, and Gi protein, and it was mediated by α2A/D-adrenoceptors and possibly α2B- adrenoceptors. The contraction was mediated mainly by α2B- and α1-adrenoceptors and involved the action of prostanoids. UK14304 and clonidine induced greater and smaller relaxations, respectively, than dexmedetomidine. In conclusion, depending on the concentration used and the presence of functional endothelium, dexmedetomidine may evoke both relaxation and contraction in isolated arteries. The vascular effects also vary depending on the blood vessel studied. Its vascular effect is different from that of clonidine and UK14304. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_US
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.subject.meshAorta - drug effects-
dc.subject.meshDexmedetomidine - pharmacology-
dc.subject.meshMesenteric Arteries - drug effects-
dc.subject.meshMuscle Contraction - drug effects-
dc.subject.meshMuscle Relaxation - drug effects-
dc.titleDexmedetomidine induces both relaxations and contractions, via different α2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the raten_HK
dc.typeArticleen_HK
dc.identifier.emailMan, RYK: rykman@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.emailNg, KFJ: jkfng@hkucc.hku.hken_HK
dc.identifier.authorityMan, RYK=rp00236en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.identifier.authorityNg, KFJ=rp00544en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1124/jpet.110.170688en_HK
dc.identifier.pmid20837990-
dc.identifier.scopuseid_2-s2.0-78649549070en_HK
dc.identifier.hkuros186072en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649549070&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume335en_HK
dc.identifier.issue3en_HK
dc.identifier.spage659en_HK
dc.identifier.epage664en_HK
dc.identifier.isiWOS:000284308800016-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectVascular effects of dexmedetomidine-
dc.identifier.scopusauthoridWong, ESW=37035429000en_HK
dc.identifier.scopusauthoridMan, RYK=7004986435en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridNg, KFJ=13608809400en_HK

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