1 Human saphenous veins were used to assess the cooperative participation of adenosine 5-triphosphate (ATP), neuropeptide Y (NPY), and noradrenaline (NA) in the vasomotor responses elicited following electrical depolarization of the perivascular nerve terminals. Rings from recently dissected human biopsies were mounted to record isometric muscular contractions; the motor activity elicited in the circular muscle layer following electrical depolarization (2.5 ± 20 Hz, 50 V, 0.5 msec) were recorded. 2 Incubation of the biopsies with either 100 nM tetrodotoxin (TTX) or 1 mM guanethidine abolished the vasomotor response elicited by electrical nerve depolarization. The independent application of either ATP or NA to vein rings induced concentration-dependent contractions. 3 Tissue incubation with 30 mM suramin or 10 nM prazosin produced 10 fold rightward displacements of the a,b-methylene ATP and NA concentration-response curves respectively. NPY contracted a limited number of biopsies, the vasoconstriction elicited was completely blocked by 1 mM BIBP 3226. A 5 min incubation of the biopsies with 10 ± 100 nM NPY synergized, in a concentration-dependent fashion, both the ATP and the ATP analogue-induced contractions. Likewise, tissue preincubation with 10 nM NPY potentiated the vasomotor responses evoked with 20 ± 60 nM NA. 4 Neither suramin, BIBP 3226, nor prazosin was individually able to signi®cantly modify the derived frequency-tension curves. In contrast, the co-application of 30 mM suramin and 10 nM prazosin or 30 mM suramin and 1 mM BIBP 3226, elicited a signi®cant (P50.01) downward displacement of the respective frequency-tension curves. 5 The simultaneous application of the three antagonists ± 30 mM suramin, 1 mM BIBP 3226 and 10 nM prazosin ± caused a signi®cantly greater displacement of the frequency-tension curve than that achieved in experiments using two of these antagonists. 6 Electrically-evoked vasomotor activity is blocked to a larger extent by tissue incubation with 2.5 mM chloroethylclonidine and 30 mM suramin rather than with 10 nM 5 methyl urapidil and 30 mM suramin. As a result, the a 1 -adrenoceptor involved in the vasomotor activity has tentatively been associated with the a 1B adrenoceptor family subtype. 7 Results support the physiological role of ATP in sympathetic neurotransmission. The present results are consistent with the working hypothesis that human sympathetic vasomotor re¯exes involve the coordinated motor action of ATP, NPY, and NA acting on vascular smooth muscle cells. The present results support the concept of sympathetic co-transmission in the human saphenous vein.

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