GW1229, A NOVEL NEUROPEPTIDE-Y Y-1 RECEPTOR ANTAGONIST, INHIBITS THE VASOCONSTRICTOR EFFECT OF NEUROPEPTIDE-Y IN THE HAMSTER MICROCIRCULATION

We studied the effect of GW1229, a novel neuropeptide Y Y-1 receptor a ntagonist, on the vasoconstriction induced by neuropeptide Y and struc turally related analogs in the hamster cheek pouch microcirculation. C hanges in arteriolar diameter and microvascular conductance were asses sed by intravital microscopy and measurement of sodium(22) clearance. GW1229 did not affect basal vascular conductance but inhibited, concen tration dependently, the reduction in arteriolar diameter and vascular conductance induced by 100 nM neuropeptide Y. GW1229 also counteracte d the vasoconstrictor effect of 100 nM [Leu(31),Pro(34)]neuropeptide Y , and that of 300 nM neuropeptide Y-(13-36). In contrast, GW1229 had n o effect on the vasoconstriction induced by noradrenaline. We conclude that the vasoconstrictor effect of neuropeptide Y in the hamster chee k pouch is mediated by neuropeptide Y Y-1 receptors. The maintenance o f physiological tone in this vascular bed does not involve the partici pation of endogenous neuropeptide Y.