Subconstrictor Doses of Neuropeptide Y Potentiate α ₁ -Adrenergic Venoconstriction In Vivo

Abstract

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.

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

“…2D), it is likely that Ang II-mediated MAPK activation occurs through different pathways than those activated by NPY and PE. This is in contrast to what was observed for PE-and Ang II-stimulated contractile responses, which both are potentiated by NPY (6)(7)(8). In addition, the NPY effect on vasoconstriction appears to occur through a PKC-dependent pathway (12).…”

“…For instance, blocking ERK protein synthesis using antisense oligodeoxynucleotides reduces transcriptional and morphological responses to PE in rat cardiomyocytes (30). NPY has been shown to potentiate the effects of various vasoactive substances including ␣-receptor agonists (6,8). NPY could potentiate the activation of PLC, leading to increased IP3 accumulation (31,32).…”

“…NPY has been implicated in various physiological responses including cardiovascular regulation (4) and the control of food intake (5). NPY is thought to play a role in cardiovascular homeostasis because it exerts a direct vasoconstrictive effect on blood vessels and can potentiate the action of other vasoactive substances such as ␣-adrenergic agonists and angiotensin II (6)(7)(8).…”

Sex-related effects on venous compliance and capillary filtration in the lower limb

“…Although in vivo experiments on human hand veins have provided evidence for sympathetic constrictor responses both via ␣ 1 -adrenoreceptor agonists and neuropeptide Y (29), no evidence exists to our knowledge that active constriction of capacitance vessels in skeletal muscle (40 -50% of the body weight) provides an important target of sympathetic responses. Thus the main part of the venous reservoir is adjusted simply by means of passive changes.…”

Neuropeptide Y and neurovascular control in skeletal muscle and skin

“…NPY potentiates ␣-adrenergic vasoconstriction in both in vivo (17,59,88) and in vitro (11,27,28,36,105) preparations. The synergistic interaction between NPY and NE is receptor mediated.…”