[Relaxation of canine pulmonary arteries caused by stimulation of atypical beta-adrenergic receptors].
To examine possible contributions of beta(3)-adrenoceptors to catecholamine-induced pulmonary vasodilation, we studied isolated canine pulmonary arterial segments under isometric conditions. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 50 mM KCl; the rank order of potency was isoproterenol (ISO, 1) > salbutamol (SAL, 0.97) > selective beta(3)-adrenoceptor agonists CL 316243 (CL, 0.87) and BRL 37344 (BRL, 0.86). Relaxant responses to SAL were competitively antagonized by the beta(2)-adrenoceptor antagonist ICI 118551 and the pA2 value was 6.67 +/- 0.21 (mean +/- SE), whereas the response to CL was weekly antagonized only by a high concentration of ICI 118551 (10(-5) M) and the apparent pA2 value was 5.24 when alpha-and beta(1)-adrenergic receptors were blocked. By contrast, the atypical beta-adrenoceptor antagonist cyanopindolol antagonized CL-induced relaxation in a competitive manner; the pA2 value was 6.71 +/- 0.12, which was lower than that with salbutamol (p < 0.05). Intracellular cyclic AMP levels were increased in a contraction-dependent manner by CL. These results suggest that beta(3)-adrenoceptors may exist in canine pulmonary arterial smooth muscle and that stimulation of this atypical receptor causes vasodilation through a cyclic AMP-dependent pathway.
Tagaya
E
E
First Department of Medicine, Tokyo Womens Medical College.
Tamaoki
J
J
Takemura
H
H
Isono
K
K
Nagai
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C057368:BRL 37344; D000242:Cyclic AMP