α2B-adrenoceptor agonist ST-91 antagonizes β2-adrenoceptor-mediated relaxation in rat mesenteric artery rings

We sought an isolated vascular preparation and experimental setting where the function of α2B-adrenoceptors could be demonstrated by non-recombinant technique. ST-91 (2-[2,6-diethylphenylamino]-2-imidazoline), an α2B-adrenoceptor agonist with a mixed α adrenergic receptor type/subtype selection profile antagonized the relaxant effect of isoproterenol in endothelium-denuded rat mesenteric artery rings precontracted with phenylephrine. At 10− 7 M of ST-91, the antagonism was characterized by a rightward shift of isoproterenol dose–response curve (A50 = 6.81 ± 1.40 e− 7 (n = 4) vs the control 1.29 ± 0.25 e− 7 M (n = 4)) with no Emax depression. At 10− 6 M the Emax depression was prevalent (36.1 ± 7.0% (n = 4) vs the control 79.9 ± 5.1% (n = 4)); both actions could be antagonized by the α2-adrenoceptor antagonist yohimbine. The not subtype-selective α2-adrenoceptor agonist xylazine (10− 7 M) did not affect the relaxant action of isoproterenol. Present findings are discussed in the light of previously reported hemodynamic effects attributed to α2B-adrenoceptors in receptor subtype-knockout animals.