Carteolol, a non-conventional partial agonist of β1-adrenoceptors, relaxes phenylephrine-constricted rat aorta through antagonism at α1-adrenoceptors

Abstract This in vitro study was designed to investigate whether carteolol, a non-conventional partial agonists of β 1 -adrenoceptors, relaxes phenylephrine-constricted rat aorta through activation of the low-affinity state of β 1 -adrenoceptors or antagonist effect at α 1 -adrenoceptors. Carteolol-induced complete concentration-dependent relaxation of phenylephrine-contracted aorta (pD 2  = 3.65 ± 0.04), this effect not being modified by endothelium removal and not antagonised by NO-synthase inhibitor N G -nitro- l -arginine methyl ester (100 µM) or cyclo-oxygenase inhibitor indomethacin (10 µM). The effect of carteolol was unaffected by the non-selective β-adrenoceptor antagonist propranolol (1 µM), or the β 2 -adrenoceptor selective antagonist (±)-1-[2,3-(dihydro-7-methyl-1 H -inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551, 1 µM). Increasing concentrations of carteolol produced a parallel rightward shift of the concentration–response curves for phenylephrine-induced contraction, exhibiting a p K B of 4.28 ± 0.07. Carteolol affinity for α 1 -adrenoceptors was evaluated by means of competition experiments carried out in BHK-21 cell membranes expressing rat recombinant α 1D -adrenoceptor, the α 1 -adrenoceptor subtype mainly present in rat aorta. Carteolol competed monophasically with [ 3 H]prazosin, exhibiting a p K i value (3.39 ± 0.31) similar to its pD 2 and not very far from its p K B . In conclusion, this study indicates that carteolol relaxes phenylephrine-contracted aorta through its α 1 -adrenoceptor antagonist properties, excluding the possibility that the relaxant effect is due to the activation of β-adrenoceptors, particularly of the low-affinity state of β 1 -adrenoceptors, by the drug.