Influence of β-adrenoceptor agonists on the pulmonary circulation.: Effects of a β3-adrenoceptor antagonist, SR 59230A

The aims of this study were (a) to compare in the rat isolated perfused lung preparation, the effects of isoprenaline and of three beta(3)-adrenoceptors agonists, SR 59104A, (N-[(6hydroxy-1,2,3,4-tetrahydronaphtalen-(2R)-2yl)methyl]-(2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride), SR 59119A (N[(7-methoxy-1,2,3,4-tetrahydronaphtalen-(2R)-2yl)methyl]-(2R)-2-hydroxy-2-(3-chlorophenyl)ethanamine hydrochloride) and SR 58611A (ethyl({7S)-7-[(2R)-2-(3-chlorophenyl)-2-hydroxyethylamino]-5,6,7,8-tetra hydronaphtalen-2-yloxy}acetate hydrochloride) on hypoxia-induced pulmonary vasoconstriction, and (b) to investigate the potential existence of atypical beta-adrenoceptors in these effects. Propranolol (0.1 mu M) was used to antagonize beta(1)- and beta(2)-adrenoceptors whereas SR 59230A, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronapht-1-ylamino]-(2S)-2-propanol oxalate) (0.3 mu M) was used to block beta(3)-adrenoceptors. Isoprenaline and the three beta(3)-adrenoceptors agonists caused concentration-dependent relaxations during the pulmonary pressure response, Propranolol and SR 59230A inhibited the relaxant effects of isoprenaline. SR 59230A but not propranolol inhibited those of SR 59104A. Finally, propranolol and SR 59230A failed to oppose SR 59119A- and SR 58611A-induced relaxant effects. In concentrations greater than or equal to 1 mu M, SR 59230A caused per se a relaxation of the hypoxic vasoconstricted lung. These results suggest the existence of atypical beta -adrenoceptors in the rat pulmonary vessels. (C) 1998 Elsevier Science B.V. All rights reserved.