Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cyclic adenosine monophosphate-dependent pathway

To determine whether functional atypical beta-adrenoceptors (beta(3)-adreno ceptors) are present in pulmonary vascular smooth muscle, we studied isolat ed canine pulmonary arterial rings under isometric conditions in vitro. Add ition of beta-adrenoceptor agonists produced a concentration-dependent rela xation of noradrenaline-precontracted tissues, a rank order potency being i soproterenol (1) > salbutamol (0.95) > selective beta(3)-adrenoceptor agoni sts, CL 316243 (0.85), and BRL 37344 (0.83). A marked desensitization to sa lbutamol occurred by pretreatment with salbutamol but not with CL 316243. W hen beta(1)-adrenoceptors had been blocked, the relaxant responses to salbu tamol were competitively antagonized by the beta(2)-adrenoceptor antagonist ICI 118551 with a pA(2) value of 7.67 +/- 0.21 (mean +/- S.E.), but the re sponse to CL 316243 was weekly antagonized by ICI 118551 only at a high con centration of 10(-5) M, where an apparent pA(2) value was 5.24. In contrast , cyanopindolol, a nonselective beta-adrenoceptor antagonist, antagonized C L 316243-induced relaxation in a competitive manner with a pA(2) of 6.10 +/ - 0.11. This pA(2) value was lower than that when salbutamol was used as an agonist (6.69 +/- 0.14, p < 0.01). Intracellular 3',5'-cyclic adenosine mo nophosphate (cAMP) levels were increased by CL 316243 in a concentration-de pendent fashion, an effect that was not altered by ICI 118551. These result s suggest that beta(3)-adrenoceptors may exist in canine pulmonary artery s mooth muscle and that stimulation of this atypical receptor causes vasodila tion through a cAMP-dependent pathway.