NEUROPEPTIDE-Y IS A VASOCONSTRICTOR AND ADRENERGIC MODULATOR IN THE HAMSTER MICROCIRCULATION BY ACTING ON NEUROPEPTIDE Y-1 AND Y-2 RECEPTORS

The microvascular effects of neuropeptide Y, and two analogs with pref erential affinity for different neuropeptide Y receptor subtypes, were assessed by intravital microscopy on the hamster cheek pouch. The int eraction of neuropeptide Y and its analogs with noradrenaline was also studied. Superfusion with 0.1-300 nM neuropeptide Y caused a concentr ation-dependent reduction in microvascular conductance that was parall eled by reductions in arteriolar and venular diameters. These effects of neuropeptide Y were equipotent with noradrenaline, but slower to de velop and longer-lasting than that of noradrenaline. Neuropeptide Y di d not affect permeability to macromolecules, as measured by extravasat ion of fluorescent dextran. The neuropeptide Y Y-1 receptor agonist, [ Leu(31),Pro(34)]neuropeptide Y, mimicked neuropeptide Y with similar p otency but shorter duration, while neuropeptide Y-(13-36), a neuropept ide Y Y-2 receptor agonist, was at least 10-fold less potent than neur opeptide Y to induce a delayed and prolonged reduction in microvascula r conductance. The joint superfusion of 1 nM neuropeptide Y plus 0.1 m u M noradrenaline did not cause synergism, nor even summation of effec ts, but reduced the contractile effect of noradrenaline. No synergism was observed after a 10 min priming with 1 nM neuropeptide Y, followed by its joint application with 0.1 mu M noradrenaline, but a significa nt vasodilation and hyperemia ensued upon stopping noradrenaline appli cation. Priming with 1 nM [Leu(31),Pro(34)]neuropeptide Y prolonged no radrenaline vasoconstriction without evidence of hyperemia. In contras t, priming with 1 nM neuropeptide Y-(13-36) significantly antagonized noradrenaline vasoconstriction. These findings indicate that both neur opeptide Y receptor subtypes are present in arterioles and venules of the hamster, and suggest that their activation with neuropeptide Y ind uces a rapid (Y-1 receptor subtype activation) and a delayed (Y-2 rece ptor subtype activation) vasocontractile response. The interaction wit h noradrenaline is complex, without evidence for synergism, but neurop eptide Y Y-2 receptor activation seems to antagonize noradrenaline and /or to facilitate auto-regulatory vasodilation after the catecholamine -induced vasoconstriction.