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Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

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dc.contributor.author변효진-
dc.date.accessioned2018-07-20T07:56:16Z-
dc.date.available2018-07-20T07:56:16Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/160686-
dc.description.abstractThe goal of this in vitro study was to examine the effect of the alpha-2 adrenoceptor agonist dexmedetomidine on phenylephrine (alpha-1 adrenoceptor agonist)-induced contraction in isolated rat aortae and to elucidate the associated cellular mechanisms, with a particular focus on alpha-1 adrenoceptor antagonism. Dexmedetomidine dose-response curves were generated in isolated endothelium-intact and endothelium-denuded rat aortae precontracted with phenylephrine or 5-hydroxytryptamine. Endothelium-denuded aortic rings were pretreated with either dexmedetomidine or the reversible alpha-1 adrenoceptor antagonist phentolamine, followed by post-treatment with the irreversible alpha-1 adrenoceptor blocker phenoxybenzamine. Control rings were treated with phenoxybenzamine alone. All rings were repeatedly washed with Krebs solution to remove all pretreatment drugs, including phenoxybenzamine, phentolamine and dexmedetomidine. Phenylephrine dose-response curves were then generated. The effect of rauwolscine on the dexmedetomidine-mediated change in phenylephrine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined using western blotting. The magnitude of the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction was higher in endothelium-intact aortae than in endothelium-denuded aortae or endothelium-intact aortae treated with Nω-nitro-L-arginine methyl ester. However, dexmedetomidine did not significantly alter 5-hydroxytryptamine-induced contraction. In further experiments, prazosin attenuated dexmedetomidine-induced contraction. Additionally, pretreatment with either dexmedetomidine plus phenoxybenzamine or phentolamine plus phenoxybenzamine produced greater phenylephrine-induced contraction than phenoxybenzamine alone, suggesting that dexmedetomidine protects aortae from the alpha-1 adrenoceptor blockade induced by phenoxybenzamine. Rauwolscine attenuated the dexmedetomidine-mediated enhancement of phenylephrine-induced eNOS phosphorylation. Taken together, these results suggest that dexmedetomidine attenuates phenylephrine-induced contractions via alpha-1 adrenoceptor blockade and endothelial nitric oxide release in the isolated rat aorta.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherIvyspring International Publisher-
dc.relation.isPartOfInternational Journal of Medical Sciences-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdrenergic Agonists/pharmacology-
dc.subject.MESHAnimals-
dc.subject.MESHAorta/drug effects*-
dc.subject.MESHAorta/metabolism*-
dc.subject.MESHDexmedetomidine/pharmacology*-
dc.subject.MESHIn Vitro Techniques-
dc.subject.MESHMale-
dc.subject.MESHMuscle Contraction/drug effects-
dc.subject.MESHNitric Oxide/metabolism*-
dc.subject.MESHPhenoxybenzamine/pharmacology-
dc.subject.MESHPhenylephrine/pharmacology*-
dc.subject.MESHRats-
dc.subject.MESHReceptors, Adrenergic/metabolism*-
dc.subject.MESHSerotonin/pharmacology-
dc.titleDexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Anesthesiology and Pain Medicine-
dc.contributor.googleauthorHyo-Jin Byon-
dc.contributor.googleauthorSeong-Ho Ok-
dc.contributor.googleauthorSoo Hee Lee-
dc.contributor.googleauthorSebin Kang-
dc.contributor.googleauthorYoungil Cho-
dc.contributor.googleauthorJeong Yeol Han-
dc.contributor.googleauthorJu-Tae Sohn-
dc.identifier.doi10.7150/ijms.17456-
dc.contributor.localIdA01863-
dc.relation.journalcodeJ02917-
dc.identifier.eissn1449-1907-
dc.identifier.pmid28260990-
dc.subject.keywordalpha-1 adrenoceptor-
dc.subject.keywordalpha-2 adrenoceptor agonist-
dc.subject.keywordaorta-
dc.subject.keywordcontraction-
dc.subject.keyworddexmedetomidine-
dc.subject.keywordnitric oxide-
dc.subject.keywordphenoxybenzamine-
dc.subject.keywordphentolamine-
dc.subject.keywordphenylephrine-
dc.contributor.alternativeNameByon, Hyo Jin-
dc.contributor.affiliatedAuthorByon, Hyo Jin-
dc.citation.volume14-
dc.citation.number2-
dc.citation.startPage143-
dc.citation.endPage149-
dc.identifier.bibliographicCitationInternational Journal of Medical Sciences, Vol.14(2) : 143-149, 2017-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers

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