The aims of this study were (a) to compare in the rat isolated perfused lung preparation, the effects of
isoprenaline and of three beta3-adrenoceptors agonists,
SR 59104A, (N-[(6hydroxy-1,2,3,4-tetrahydronaphtalen-(2 R)-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-tetrahydronaphtalen-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 microM) was used to antagonize beta1- and beta2-adrenoceptors whereas
SR 59230A, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronapht-1-ylam ino]-(2S)-
2-propanol oxalate) (0.3 microM) was used to block beta3-
adrenoceptors.
Isoprenaline and the three beta3-
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 > or = 1 microM,
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.