Adrenergic mechanisms in canine intralobar pulmonary arteries and veins.
The responses of canine intralobar pulmonary arteries (IPA) and veins (IPV) to transmural nerve stimulation (TNS), and exogenously administered norepinephrine (NE) were studied to evaluate the alpha-adrenergic neuroeffector system in the canine pulmonary vasculature. IPA and IPV elicited contractions in response to both NE (10(-10) to 10(-5) M) and TNS (0.5-32 Hz, 2 ms duration and delay). The equilibrium (steady state) contractile responses of IPA and IPV to TNS were abolished with the adrenergic neuronal blocking agents guanethidine and bretylium and the depolarization blocking agent tetrodotoxin in concentrations which did not affect the responses to NE or KCl. The contractile responses of IPA and IPV to TNS and NE were reduced in a concentration-dependent way, by the alpha-adrenergic receptor-blocking agents phentolamine, tolazoline and clonidine. The contractile responses of IPA and IPV to TNS and NE were enhanced after inhibition of neuronal reuptake of NE (uptake1) with cocaine, as well as after blockade of extraneuronal reuptake of NE (uptake2) with hydrocortisone. Analysis of the equilibrium responses of the IPA and IPV to TNS and NE with an Arunlakshana-Schild plot to define the concentration of alpha 1-receptor antagonists necessary to double the ED50 for TNS and NE (defined as the pA2), demonstrated that the postsynaptic alpha-receptors of IPV differed from that of IPA. These data support the conclusions that IPA and IPV 1) contain a functional adrenergic innervation and neuroeffector system, 2) contract in response to both TNS and NE, 3) demonstrate the presence of mechanisms for both uptake1 and uptake2 of NE, and 4) IPV contain postsynaptic alpha-receptors that may differ from each other.
D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000294:innervation*; D011667:Pulmonary Veins / Q000294:innervation*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014043:Tolazoline / Q000494:pharmacology
D001949:Bretylium Compounds; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D013779:Tetrodotoxin; D014043:Tolazoline; D003042:Cocaine; D003000:Clonidine; D010646:Phentolamine; D006145:Guanethidine