Presynaptic beta 2-adrenoceptors on the sympathetic nerve fibres of the human saphenous vein: no evidence for involvement in adrenaline-mediated positive feedback loop regulating noradrenergic transmission.

Abstract

Spirally cut strips of human saphenous veins preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and, unless stated otherwise, of cocaine or desipramine. Tritium overflow was stimulated electrically (2 Hz). Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential beta 2-adrenoceptor agonist procaterol concentration-dependently increased the electrically evoked tritium overflow. Prenalterol, a beta-adrenoceptor agonist with moderate preference for beta 1-adrenoceptors, was ineffective. The concentration-response curve of isoprenaline was shifted to the right by the nonselective beta-adrenoceptor antagonist propranolol and by the preferential beta 2-adrenoceptor antagonist ICI 118,551, but was not affected by the beta 1-selective antagonist atenolol. In experiments on strips preexposed to adrenaline 10 nmol/l (i.e. a concentration higher than that which normally occurs in vivo) for 32 min in the absence of cocaine or desipramine, the electrically evoked 3H overflow was not affected 12 and 44 min after withdrawal of adrenaline, irrespective of whether propranolol was absent or present in the superfusion fluid. In veins incubated with 3H-adrenaline, a considerable amount of the radioactivity was accumulated. During subsequent superfusion with 3H-adrenaline-free solution, electrical stimulation induced tritium overflow in a tetrodotoxin-sensitive manner. Propranolol failed to modify the evoked tritium overflow. It is concluded that the sympathetic nerve fibres of the human saphenous vein are endowed with facilitatory presynaptic beta 2-adrenoceptors. These receptors do not seem to play a substantial role in a local adrenaline (previously taken up)-mediated positive feedback loop regulating noradrenergic transmission, at least under the present in vitro conditions.