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 intraarterially 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 a-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 Y-1 receptor agonist, (Leu(31), Pro(34)) Npy were identical to those of NPY. The Y-2 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 (Leu(31), Pro(34)) NPY, but not NPY13-36, produced significant presser effects. These data suggest that: 1) NPY produces neurogenic cutaneous vasodilation via presynaptic Y-2 receptor-mediated inhibition of sympathetic tone, 2) Y-1 receptors may also exist presynaptically, however, it is likely that (Leu(31), Pro(34)) NPY does not distinguish between Y-1 and Y-2 receptors, and 3) activation of postsynaptic Y-1 receptors produces vasoconstriction which is unmasked only when the noradrenergic tone is eliminated.