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

Abstract

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.