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.