PHARMACOLOGICAL ANALYSIS OF NOREPINEPHRINE RESPONSES IN RABBIT PULMONARY BLOOD-VESSELS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 224  (3) , 579-589
Abstract
Drug effects were examined on cumulative norepinephrine (NE) concentration-response curves in ring segments of right extrapulmonary artery, intrapulmonary artery (IPA) and intrapulmonary vein (IPV) isolated from rabbit lung. Phentolamine (0.1 and 1.0 .mu.M) caused concentration-dependent nonparallel rightward shifts in NE concentration-response curves and decreased maximal tension development in IPA by as much as 84%. Propranolol (3 .mu.M) significantly increased the maximal developed tension to NE in IPA and IPV by 49 and 27%, respectively, and also abolished the relaxation response to higher (10-6-10-4 M) concentrations of NE observed in control experiments. Apparently, responses of pulmonary vessels to NE, in particular IPA and IPV, consisted of an initial contractile response (.alpha.-adrenergic receptor mediated) followed by .beta.-adrenergic receptor-mediated relaxation which functionally opposed the contractile response to NE. Contractile response to high concentrations of NE (> 10-4 M) were unaffected. Inhibition of neuronal uptake of NE by cocaine (10 .mu.M) significantly potentiated NE contractile response in right extrapulmonary artery, IPA and IPV. Inhibition of extraneuronal uptake of NE by hydrocortisone (30 .mu.M) or monoamine oxidase inhibition by harmaline (1 .mu.M) did not alter contractile response to NE. Although the catechol-O-methyl-transferase inhibitor U-0521 [3'',4''-dihydroxy-.alpha.-methylpropiophenone] (100 .mu.M) also failed to potentiate NE contractile effects, this drug significantly decreased the initial contractile response to low concentrations of NE and greatly attenuated contractile respones to high concentrations of NE (> 10-4 M) in IPA and IPV. Rabbit intrapulmonary vessels show enhanced .beta.-adrenergic receptor-mediated effects when compared with extrapulmonary vessels.