Pharmacological analysis of norepinephrine responses in rabbit pulmonary blood vessels

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 microM) 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 microM) 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) to 10(-4) M) concentrations of NE observed in control experiments. These data suggested that 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 (greater than 10(-4) M) were unaffected. Inhibition of neuronal uptake of NE by cocaine (10 microM) significantly potentiated NE contractile response in right extrapulmonary artery, IPA and IPV. Inhibition of extraneuronal uptake of NE by hydrocortisone (30 microM) or monoamine oxidase inhibition by harmaline (1 microM) did not alter contractile response to NE. Although the catechol-O-methyl-transferase inhibitor U-0521 (100 microM) also failed to potentiate NE contractile effects, this drug significantly decreased the initial contractile response to low concentrations of NE and greatly attenuated contractile responses to high concentrations of NE (greater than 10(-4) M) in IPA and IPV. These results indicate that rabbit intrapulmonary vessels show enhanced beta adrenergic receptor-mediated effects when compared with extrapulmonary vessels.