Influence of beta-adrenoceptor agonists on the pulmonary circulation. Effects of a beta3-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 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.
Dumas
M
M
Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaires Expérimentales, Faculté de Médecine, Dijon, France.
Dumas
J P
JP
Bardou
M
M
Rochette
L
L
Advenier
C
C
Giudicelli
J F
JF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C114929:SR 59104A; C114930:SR 59119A; D013764:Tetrahydronaphthalenes; D011433:Propranolol; D007545:Isoproterenol; C076252:amibegron