Neuronally released norepinephrine does not preferentially activate postjunctional alpha 1-adrenoceptors in human blood vessels in vitro.
Human isolated digital arteries and metatarsal veins, obtained postmortem, have been used to compare the effects of alpha-adrenoceptor antagonists on contractile responses to nerve stimulation. The antagonists used were prazosin, rauwolscine, BE 2254, and yohimbine. Rauwolscine (alpha 2-antagonist), as well as prazosin and BE 2254 (alpha 1-antagonists), in concentrations of 10(-9), 10(-8), and 10(-7) mol/liter, potently antagonized the frequency-response curves to nerve stimulation. Yohimbine (alpha 2-antagonist) was slightly less potent, failing to antagonize responses to nerve stimulation in arteries at the concentration of 10(-9) mol/liter significantly, but producing potent antagonism of responses in both arteries and veins at higher concentrations (10(-8), 10(-7) mol/liter). All antagonists inhibited the contractile responses to nerve stimulation to a greater extent in veins than in arteries. Rauwolscine (10(-9), 10(-8), and 10(-7) mol/liter) and BE 2254 (10(-7) but not 10(-8) mol/liter) significantly enhanced stimulation-induced tritium efflux in arteries and veins. These results suggest that alpha 2-adrenoceptor antagonists, despite their prejunctional effects, are potent antagonists of contractile responses to nerve stimulation. Thus, in these human blood vessels, endogenously released norepinephrine does not preferentially activate postjunctional alpha 1-adrenoceptors, but activates receptors with the properties of both the alpha 1- and alpha 2-adrenoceptor subtypes.
Stevens
M J
MJ
Moulds
R F
RF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D044024:Tetralones; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D015016:Yohimbine; C010652:BE 2254; D009638:Norepinephrine; D011224:Prazosin