Subconstrictor doses of neuropeptide Y potentiate alpha 1-adrenergic venoconstriction in vivo.
The 36-amino acid human neuropeptide Y is a vasoactive compound released after stimulation of the sympathetic nervous system. In addition to its direct and long-lasting vasopressor effects, it may potentiate the constrictor action of catecholamines and other vasoconstrictors at doses that do not per se exert vascular effects. Using the hand vein compliance technique, we have previously shown that neuropeptide Y also constricts superficial hand veins and that its effects may last for several hours. In this study, we investigated the local effect of neuropeptide Y on alpha 1-adrenergic venoconstriction in nine healthy volunteers 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 constructed, and the responses were fitted to a four-parameter logistic equation. Neuropeptide Y dose dependently shifted the phenylephrine curves toward lower dose rates without affecting maximal effects. ED50 values 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, respectively. Comparison with neuropeptide Y dose-response curves revealed that the interaction was synergistic. These are the first data in humans to show that small dose rates of neuropeptide Y may potentiate alpha-adrenergic effects in vivo. Because this interaction occurs at estimated local concentrations nearly achieved in humans, these studies suggest that neuropeptide Y might modulate the filling of this capacitance system in vivo.
Linder
L
L
Department of Internal Medicine, University Hospital Basel, Switzerland.
Lautenschlager
B M
BM
Haefeli
W E
WE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D004357:Drug Synergism; D005260:Female; D006225:Hand / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014661:Vasoconstriction; D014680:Veins / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010656:Phenylephrine