A study of ATP as a sympathetic cotransmitter in human saphenous vein

1 Strips of human saphenous veins were superfused with Krebs‐Henseleit solution at either 25°C or 37°C. Constrictor responses to electrical stimulation (10 Hz, 40 s) but not to exogenous noradrenaline (0.1, 1 μ m ) were abolished by guanethidine (10 μ m ) and tetrodotoxin (1 μ m ). Hence, responses to electrical stimulation are due to action potential‐induced release of sympathetic neurotransmitters. 2 Constrictor responses to electrical stimulation and noradrenaline were reduced by the α 1 ‐adrenoceptor antagonist, prazosin (0.3 μ m ) as well as by the α 2 ‐adrenoceptor antagonist, rauwolscine (1 μ m ). The combination of prazosin and rauwolscine abolished constrictor responses to noradrenaline at 25°C and 37°C. However, constrictor responses to electrical stimulation were partly resistant to α‐adrenoceptor blockade by prazosin and rauwolscine (at 25°C about 30%). Residual constrictor responses to electrical stimulation were also observed in the presence of the combination of prazosin (3 μ m ) and rauwolscine (10 μ m ) as well as in the presence of phenoxybenzamine (10 μ m ). 3 Veins, incubated with [ 3 H]‐noradrenaline, released tritium upon electrical stimulation (10 Hz, 40 s). Moreover, electrical stimulation also induced an overflow of ATP amounting to 4.8 ± 1.5 pmol g −1 at 25°C and 2.0 ± 0.5 pmol g −1 at 37°C. Both tritium and ATP overflow were abolished by tetrodotoxin (0.5 μ m ). The combination of prazosin (0.3 μ m ) and rauwolscine (1 μ m ) increased tritium overflow at either 25°C or 37°C by about 120%, but reduced ATP overflow by about 70%. Hence, a significant percentage of the electrically evoked ATP overflow seems to be released from non‐neuronal cells upon activation of α‐adrenoceptors by endogenous noradrenaline. The remaining ATP overflow, which was resistant to α‐adrenoceptor blockade, may reflect neuronally released ATP. 4 ATP (300 μ m ) and α,β‐methylene‐ATP (1, 10 μ m ), both induced constrictor responses. The P 2 ‐purinoceptor antagonist, suramin (300 μ m ) markedly inhibited constrictor responses to ATP and α,β‐methylene‐ATP, but not those to electrical stimulation and to noradrenaline. Moreover, suramin (300 μ m ) failed to diminish the α‐adrenoceptor blockade‐resistant constrictor response to 10 Hz. 5 In conclusion, constrictor responses to sympathetic nerve stimulation in human saphenous veins are mainly but not exclusively mediated by neuronally released noradrenaline. There is a concomitant release of ATP and noradrenaline. P 2 ‐purinoceptors which mediate vasoconstriction are present; however, a role of neuronally released ATP in constrictor responses to electrical stimulation could not be established. Therefore, the nature of the sympathetic transmitter responsible for α‐adrenoceptor blockade‐resistant constrictor responses remains unknown.