DIRECT EVIDENCE FOR THE ROLE OF NEUROPEPTIDE-Y IN SYMPATHETIC-NERVE STIMULATION-INDUCED VASOCONSTRICTION

Neuropeptide Y (NPY) is a vasoconstrictor peptide and a cotransmitter with norepinephrine (NE) in sympathetic nerve terminals and is thought to be involved in sympathetic nerve stimulation (SNS)-induced vasocon striction. Using BIBP-3226, a Y-1 receptor selective antagonist, we ex amined this hypothesis in the isolated and perfused mesenteric vascula r bed. SNS produced a frequency-dependent increase in perfusion pressu re and concomitant overflow of NPY immunoreactivity in the perfusate. [Leu(31), Pro(34)]Npy potentiated NE-induced and ATP-induced vasoconst riction, indicating the presence and biological action of Y-1 receptor s in this vascular bed. The potentiation effect of [Leu(31),Pro(34)]Np y of the increase in perfusion pressure by NE, ATP, or SNS was prevent ed by BIBP-3226. In addition, SNS-induced vasoconstriction at both hig h and low frequencies was significantly attenuated by BIBP-3226 at a c oncentration that completely blocked the [Leu(31),Pro(34)]Npy- induced potentiation of the NE- or ATP-induced vasoconstrictor effect. These results suggest that similar to 30% of vasoconstriction produced by SN S depends on NPY in the mesenteric vascular bed.