Adenosine 5 '-triphosphate and neuropeptide Y are co-transmitters in conjunction with noradrenaline in the human saphenous vein

1 Human saphenous veins were used to assess the cooperative participation o f 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 b iopsies were mounted to record isometric muscular contractions; the motor a ctivity elicited in the circular muscle layer following electrical depolari zation (2.5-20 Hz, 50 V, 0.5 msec) were recorded. 2 Incubation of the biopsies with either 100 nM tetrodotoxin (TTX) or 1 mu M guanethidine abolished the vasomotor response elicited by electrical nerv e depolarization. The independent application of either ATP or NA to vein r ings induced concentration-dependent contractions. 3 Tissue incubation with 30 mu M suramin or 10 nM prazosin produced 10 fold rightward displacements of the alpha,beta-methylene ATP and NA concentrati on-response curves respectively. NPY contracted a limited number of biopsie s, the vasoconstriction elicited was completely blocked by 1 mu M BIBP 3226 . A 5 min incubation of the biopsies with 10-100 nM NPY synergized, in a co ncentration-dependent fashion, both the ATP and the ATP analogue-induced co ntractions. Likewise, tissue preincubation with 10 nM NPY potentiated the v asomotor responses evoked with 20-60 nM NA. 4 Neither suramin, BIBP 3226, nor prazosin was individually able to signifi cantly modify the derived frequency-tension curves. In contrast, the co-app lication of 30 mu M suramin and 10 nM prazosin or 30 mu M suramin and 1 mu M BIBP 3226, elicited a significant (P < 0.01) downward displacement of the respective frequency-tension curves. 5 The simultaneous application of the three antagonists-30 mu M suramin, 1 mu M BIBP 3226 and 10 nM prazosin-caused a significantly greater displaceme nt of the frequency-tension curve than that achieved in experiments using t wo of these antagonists. 6 Electrically-evoked vasomotor activity is blocked to a larger extent by t issue incubation with 2.5 mu M chloroethylclonidine and 30 mu M suramin rat her than with 10 nM 5 methyl urapidil and 30 mu M suramin. As a result, the alpha(1)-adrenoceptor involved in the vasomotor activity has tentatively b een associated with the alpha(1B) adrenoceptor family subtype. 7 Results support the physiological role of ATP in sympathetic neurotransmi ssion. The present results are consistent with the working hypothesis that human sympathetic vasomotor reflexes involve the coordinated motor action o f ATP, NPY, and NA. acting on vascular smooth muscle cells. The present res ults support the concept of sympathetic co-transmission in the human saphen ous vein.