RGD Reference Report - Dexmedetomidine induces both relaxations and contractions, via different {alpha}2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the rat. - Rat Genome Database

RGD Reference Report - Dexmedetomidine induces both relaxations and contractions, via different {alpha}2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the rat. - Rat Genome Database

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Dexmedetomidine induces both relaxations and contractions, via different {alpha}2-adrenoceptor subtypes, in the isolated mesenteric artery and aorta of the rat.
Authors:	Wong, ES Man, RY Vanhoutte, PM Ng, KF
Citation:	Wong ES, etal., J Pharmacol Exp Ther. 2010 Dec;335(3):659-64. Epub 2010 Sep 13.
RGD ID:	6480489
Pubmed:	PMID:20837990 (View Abstract at PubMed)
DOI:	DOI:10.1124/jpet.110.170688 (Journal Full-text)
Dexmedetomidine is an alpha(2)-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-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha) (U46619) in the presence or absence of indomethacin; N(omega)-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)-isoquinol indione 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]prop ionic 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 G(i) protein, and it was mediated by alpha(2A/D)-adrenoceptors and possibly alpha(2B)-adrenoceptors. The contraction was mediated mainly by alpha(2B)- and alpha(1)-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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
vasodilation		IDA		6480489		RGD

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Genes (Rattus norvegicus)

Adra2a (adrenoceptor alpha 2A)

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