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Martínez-Salas, S.G; Campos-Peralta, J.M; Pardo, J.P; Hernández-Muñoz, R; Ibarra, M; Tanoue, A; Tsujimoto, G; Villalobos-Molina, R (2011)

? 1D-ADRENOCEPTOR REGULATES THE VASOPRESSOR ACTION OF ? 1A-ADRENOCEPTOR IN MESENTERIC VASCULAR BED OF ? 1D-ADRENOCEPTOR KNOCKOUT MICE

Auton. Autacoid Pharmacol. 31(3-4):64-71
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1 The pressor action of the ? 1A-adrenoceptor (? 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 ? 1-ARs agonist phenylephrine and their blockade by selective ? 1-ARs antagonists in the isolated mesenteric vascular bed of wild-type (WT) mice and ? 1D-AR knockout (KO ? 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 ? 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 ? 1D-AR mice. 4 Because of its high affinity, low concentrations of the ? 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 ? 1D-AR mice. 5 The ? 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 ? 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 ? 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 ? 1D-AR mice expresses ? 1A-AR, that the pressor action of ? 1A-AR is up-regulated for ? 1D-AR in WT mice and suggest an important role of ? 1B-AR in the vascular pressure evoked by phenylephrine in KO ? 1D-AR mice. © 2011 Blackwell Publishing Ltd.