Modulation of noradrenaline release in human saphenous vein via presynaptic alpha 2-adrenoceptors

Strips of human saphenous veins were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing cocaine, corticosterone and propranolol. The electrically (6 Hz) evoked overflow of tritium (78% of which was accounted for by unmetabolized [3H]noradrenaline) was abolished by tetrodotoxin or omission of Ca2+ from the superfusion fluid. Unlabelled noradrenaline, alpha-methylnoradrenaline, B-HT 920 and clonidine inhibited the evoked overflow (maximum effect of clonidine lower than that of the other compounds) whereas methoxamine was ineffective. The alpha 2-adrenoceptor antagonists, BDF 6143 and rauwolscine, facilitated the evoked overflow but no effect was obtained with prazosin. Rauwolscine produced a shift to the right of the concentration-response curve of B-HT 920 for its inhibitory effect on evoked outflow and BDF 6143 caused a shift to the right of the corresponding curve of clonidine. It is concluded that the stimulation-evoked release of noradrenaline from the sympathetic nerve fibres of the human saphenous vein is modulated via presynaptic alpha 2-adrenoceptors.