title: α(1D)-Adrenoceptor regulates the vasopressor action of α(1A)-adrenoceptor in mesenteric vascular bed of α(1D)-adrenoceptor knockout mice.
abstract: 1 The pressor action of the α(1A)-adrenoceptor (α(1A)-AR) agonist A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) and the α(1)-ARs agonist phenylephrine and their blockade by selective α(1)-ARs antagonists in the isolated mesenteric vascular bed of wild-type (WT) mice and α(1D)-AR knockout (KO α(1D)-AR) mice were evaluated. 2 The apparent potency of A61603 to increase the perfusion pressure in the mesenteric vascular bed of WT and KO α(1D)-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 α(1D)-AR mice. 4 Because of its high affinity, low concentrations of the α(1A)-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(1D)-AR mice. 5 The α(1D)-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 α(1B/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 α(1D)-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 α(1D)-AR mice expresses α(1A)-AR, that the pressor action of α(1A)-AR is up-regulated for α(1D)-AR in WT mice and suggest an important role of α(1B)-AR in the vascular pressure evoked by phenylephrine in KO α(1D)-AR mice.
authors.affiliation: Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea, Mexico.
authors.forename: S G
authors.initials: SG
authors.lastname: Martínez-Salas
authors.forename: J M
authors.initials: JM
authors.lastname: Campos-Peralta
authors.forename: J P
authors.initials: JP
authors.lastname: Pardo
authors.forename: R
authors.initials: R
authors.lastname: Hernández-Muñoz
authors.forename: M
authors.initials: M
authors.lastname: Ibarra
authors.forename: A
authors.initials: A
authors.lastname: Tanoue
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: R
authors.initials: R
authors.lastname: Villalobos-Molina
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013941:Thymine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: C094643:A 61603; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D010879:Piperazines; C120711:RS 100329; D018340:Receptors, Adrenergic, alpha-1; D013764:Tetrahydronaphthalenes; D010656:Phenylephrine; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D013941:Thymine