Alpha1A-adrenoceptors predominate in the control of blood pressure in mouse mesenteric vascular bed.
1 The pressor action of the alpha1A-adrenoceptor agonist, A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or the alpha1-adrenoceptor agonist phenylephrine, and their blockade by selective alpha1-adrenoceptor antagonists in the mouse isolated mesenteric vascular bed were evaluated. 2 A61603 showed a approximately 235-fold higher potency in elevating perfusion pressure in mesenteric bed compared to phenylephrine. 3 The alpha1A-adrenoceptor selective antagonist RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione), displaced with high affinity agonist concentration-response curves to the right in a concentration-dependent manner. 4 The alpha1D-adrenoceptor selective antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione), did not displace A61603 nor did it block the phenylephrine-induced pressor response. 5 The alpha1B/D-adrenoceptor alkylating antagonist chloroethylclonidine (CEC), caused a rightward shift of the phenylephrine concentration-response curve and reduced its maximum response; however, CEC only slightly modified A61603 evoked contraction. 6 The results indicate that the isolated mouse mesenteric vascular bed expresses alpha1A-adrenoceptors and suggest a very discrete role for 1B-adrenoceptors.
Martínez-Salas
S G
SG
Escuela Militar de Graduados de Sanidad, Universidad del Ejército y Fuerza Aérea, Secretaría de la Defensa Nacional, México, D.F.
Campos-Peralta
J M
JM
Pares-Hipolito
J
J
Gallardo-Ortíz
I A
IA
Ibarra
M
M
Villalobos-Molina
R
R
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013941:Thymine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
C094643:A 61603; C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; C547720:Adra1d protein, mouse; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; 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