Evidence against β 3 ‐adrenoceptors or low affinity state of β 1 ‐adrenoceptors mediating relaxation in rat isolated aorta

The presence of β 3 ‐adrenoceptors and the low affinity state of the β 1 ‐adrenoceptor (formerly ‘putative β 4 ‐adrenoceptor’) was investigated in ring preparations of rat isolated aorta preconstricted with phenylephrine or prostaglandin F 2α (PGF 2α ). Relaxant responses to isoprenaline, selective β 3 ‐adrenoceptor agonists (BRL 37344, SR 58611A, CL 316243) and non‐conventional partial agonists (CGP 12177A, cyanopindolol, pindolol) were obtained. In phenylephrine‐constricted, but not PGF 2α ‐constricted rings, relaxations to isoprenaline showed a propranolol‐resistant component. In phenylephrine‐constricted rings, relaxations to BRL 37344 (pEC 50 , 4.64) and SR 58611A (pEC 50 , 4.94) were not antagonized by the selective β 3 ‐adrenoceptor antagonist SR 59230A (1 μ M ). CL 316243 (100 μ M ) failed to produce relaxation. In PGF 2α ‐constricted rings only SR 58611A produced relaxation, which was not affected by SR 59230A (3 μ M ). Non‐conventional partial agonists produced relaxation in phenylephrine‐constricted but not PGF 2α ‐constricted rings. The relaxation to CGP 12177A was unaffected by SR 59230A (1 μ M ) or by CGP 20712A (10 μ M ), reported to block the low affinity state of the β 1 ‐adrenoceptor. β‐adrenoceptor antagonists also produced relaxation in phenylephrine‐constricted rings with an order of potency of (pEC 50 values): bupranolol (5.5)∼38;SR 59230A (5.47)∼38;cyanopindolol (5.47)>pindolol (5.30)>alprenolol (5.10)>propranolol (4.83)>ICI 118551 (4.60)>CGP 12177A (4.38)∼38;CGP 20712A (4.35). Bupranolol (100 μ M ), alprenolol (30 μ M ), propranolol (100 μ M ) and SR 59230A (10 μ M ) produced no relaxation in PGF 2α ‐constricted rings. These results provide no evidence for the presence of functional β 3 ‐adrenoceptors or the low affinity state of the β 1 ‐adrenoceptor in rat aorta.British Journal of Pharmacology (2003) 138 , 99–106. doi: 10.1038/sj.bjp.0705017