S. G. Martínez-Salas, J. M. Campos-Peralta, J. P. Pardo, R. Hernández-Muñoz, M. Ibarra, A. Tanoue, G. Tsujimoto, R. Villalobos-Molina
{"title":"α1D-Adrenoceptor regulates the vasopressor action of α1A-adrenoceptor in mesenteric vascular bed of α1D-adrenoceptor knockout mice","authors":"S. G. Martínez-Salas, J. M. Campos-Peralta, J. P. Pardo, R. Hernández-Muñoz, M. Ibarra, A. Tanoue, G. Tsujimoto, R. Villalobos-Molina","doi":"10.1111/j.1474-8673.2011.00468.x","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p><b>1</b> The pressor action of the α<sub>1A</sub>-adrenoceptor (α<sub>1A</sub>-AR) agonist A61603 (<i>N</i>-[5-(4,5-dihydro-1<i>H</i>-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) and the α<sub>1</sub>-ARs agonist phenylephrine and their blockade by selective α<sub>1</sub>-ARs antagonists in the isolated mesenteric vascular bed of wild-type (WT) mice and α<sub>1D</sub>-AR knockout (KO α<sub>1D</sub>-AR) mice were evaluated.</p>\n <p><b>2</b> The apparent potency of A61603 to increase the perfusion pressure in the mesenteric vascular bed of WT and KO α<sub>1D</sub>-AR mice is 86 and 138 times the affinity of phenylephrine, respectively.</p>\n <p><b>3</b> A61603 also enhanced the perfusion pressure by ≈1.7 fold in the mesenteric vascular bed of WT mice compared with KO α<sub>1D</sub>-AR mice.</p>\n <p><b>4</b> Because of its high affinity, low concentrations of the α<sub>1A</sub>-AR selective antagonist RS100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) shifted the agonist concentration–response curves to the right in the mesenteric vascular bed of WT and KO α<sub>1D</sub>-AR mice.</p>\n <p><b>5</b> The α<sub>1D</sub>-AR selective antagonist BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione) did not modify the A61603 or the phenylephrine-induced pressor effect.</p>\n <p><b>6</b> The α<sub>1B/D</sub>-ARs alkylating antagonist chloroethylclonidine (CEC) shifted the agonist concentration–response curves to the right and decreased the maximum phenylephrine-induced vascular contraction in KO α<sub>1D</sub>-AR mice when compared to WT mice; however, CEC only slightly modified the contraction induced by A61603.</p>\n <p><b>7</b> The results indicate that the isolated mesenteric vascular bed of WT and KO α<sub>1D</sub>-AR mice expresses α<sub>1A</sub>-AR, that the pressor action of α<sub>1A</sub>-AR is up-regulated for α<sub>1D</sub>-AR in WT mice and suggest an important role of α<sub>1B</sub>-AR in the vascular pressure evoked by phenylephrine in KO α<sub>1D</sub>-AR mice.</p>\n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2011-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1474-8673.2011.00468.x","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1474-8673.2011.00468.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 3
Abstract
1 The pressor action of the α1A-adrenoceptor (α1A-AR) agonist A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) and the α1-ARs agonist phenylephrine and their blockade by selective α1-ARs antagonists in the isolated mesenteric vascular bed of wild-type (WT) mice and α1D-AR knockout (KO α1D-AR) mice were evaluated.
2 The apparent potency of A61603 to increase the perfusion pressure in the mesenteric vascular bed of WT and KO α1D-AR mice is 86 and 138 times the affinity of phenylephrine, respectively.
3 A61603 also enhanced the perfusion pressure by ≈1.7 fold in the mesenteric vascular bed of WT mice compared with KO α1D-AR mice.
4 Because of its high affinity, low concentrations of the α1A-AR selective antagonist RS100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) shifted the agonist concentration–response curves to the right in the mesenteric vascular bed of WT and KO α1D-AR mice.
5 The α1D-AR selective antagonist BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione) did not modify the A61603 or the phenylephrine-induced pressor effect.
6 The α1B/D-ARs alkylating antagonist chloroethylclonidine (CEC) shifted the agonist concentration–response curves to the right and decreased the maximum phenylephrine-induced vascular contraction in KO α1D-AR mice when compared to WT mice; however, CEC only slightly modified the contraction induced by A61603.
7 The results indicate that the isolated mesenteric vascular bed of WT and KO α1D-AR mice expresses α1A-AR, that the pressor action of α1A-AR is up-regulated for α1D-AR in WT mice and suggest an important role of α1B-AR in the vascular pressure evoked by phenylephrine in KO α1D-AR mice.