SUBCONSTRICTOR DOSES OF NEUROPEPTIDE-Y POTENTIATE ALPHA(1)-ADRENERGICVENOCONSTRICTION IN-VIVO

The 36-amino acid human neuropeptide Y is a vasoactive compound releas ed after stimulation of the sympathetic nervous system. In addition to its direct and long-lasting vasopressor effects, it may potentiate th e constrictor action of catecholamines and other vasoconstrictors at d oses that do not per se exert vascular effects. Using the hand vein co mpliance technique, we have previously shown that neuropeptide Y also constricts superficial hand veins and that its effects may last for se veral hours. In this study, we investigated the local effect of neurop eptide Y on alpha(1)-adrenergic venoconstriction in nine healthy volun teers at dose rates that did not affect venous compliance. On separate days, cumulative dose-response curves to phenylephrine alone and with coadministration of 1 or 30 pmol neuropeptide Y per minute were const ructed, and the responses were fitted to a four-parameter logistic equ ation. Neuropeptide Y dose dependently shifted the phenylephrine curve s toward lower dose rates without affecting maximal effects. ED(50) va lues for phenylephrine alone and with 1 or 30 pmol/min neuropeptide Y were 4.0, 4.9 (P = NS versus control), and 1.2 (P < .005) nmol/min, re spectively. Comparison with neuropeptide Y dose-response curves reveal ed that the interaction was synergistic. These are the first data in h umans to show that small dose rates of neuropeptide Y may potentiate a -adrenergic effects in vivo. Because this interaction occurs at estima ted local concentrations nearly achieved in humans, these studies sugg est that neuropeptide Y might modulate the filling of this capacitance system in vivo.