Cutaneous vasomotor effects of neuropeptide Y.
The effects of neuropeptide Y (NPY) were examined on the cutaneous microvascular blood flow (CMF) of the hindpaws in anesthetized rats. NPY (0.5-50 nmol/kg), infused intra-arterially into the hindpaw circulation, produced sustained dose-dependent increases in CMF (29 +/- 7% to 210 +/- 52%) indicating cutaneous vasodilation. Denervation of a hindpaw, ganglionic or alpha-adrenergic blockade significantly elevated the resting CMF indicating tonic vasoconstrictor sympathetic input to the cutaneous vasculature. In the denervated hindpaw or following ganglionic blockade, NPY produced sustained decreases in CMF (up to 51 +/- 8%) indicating vasoconstriction. Effects of the Y1 receptor agonist, (Leu31, Pro34) NPY were identical to those of NPY. The Y2 receptor agonist, NPY13-36 increased CMF of the intact hindpaw (24 +/- 10%-68 +/- 16% at 5-150 nmol/kg, i.a.) but did not affect CMF of the denervated hindpaw. NPY and (Leu31, Pro34)NPY, but not NPY13-36, produced significant pressor effects. These data suggest that: 1) NPY produces neurogenic cutaneous vasodilation via presynaptic Y2 receptor-mediated inhibition of sympathetic tone, 2) Y1 receptors may also exist presynaptically, however, it is likely that (Leu31, Pro34)NPY does not distinguish between Y1 and Y2 receptors, and 3) activation of postsynaptic Y1 receptors produces vasoconstriction which is unmasked only when the noradrenergic tone is eliminated.
Hashim
M A
MA
Division of Pharmacology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.
Tadepalli
A S
AS
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D003714:Denervation; D005730:Ganglionic Blockers / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007700:Kinetics; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D005730:Ganglionic Blockers; D009478:Neuropeptide Y; D010446:Peptide Fragments; C062924:neuropeptide Y (13-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D018738:Hexamethonium; D009638:Norepinephrine