Direct evidence for the role of neuropeptide Y in sympathetic nerve stimulation-induced vasoconstriction

Department of Pharmacological and Physiological Science, Saint Louis University Health Sciences Center, St. Louis, Missouri 63104 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 vasoconstriction. Using BIBP-3226, a Y 1 receptor selective antagonist, we examined this hypothesis in the isolated and perfused mesenteric vascular bed. SNS produced a frequency-dependent increase in perfusion pressure and concomitant overflow of NPY immunoreactivity in the perfusate. [Leu 31 ,Pro 34 ]NPY potentiated NE-induced and ATP-induced vasoconstriction, indicating the presence and biological action of Y 1 receptors in this vascular bed. The potentiation effect of [Leu 31 ,Pro 34 ]NPY of the increase in perfusion pressure by NE, ATP, or SNS was prevented by BIBP-3226. In addition, SNS-induced vasoconstriction at both high and low frequencies was significantly attenuated by BIBP-3226 at a concentration that completely blocked the [Leu 31 ,Pro 34 ]NPY-induced potentiation of the NE- or ATP-induced vasoconstrictor effect. These results suggest that ~30% of vasoconstriction produced by SNS depends on NPY in the mesenteric vascular bed. BIBP-3226; neuropeptide Y release; adenosine 5'-triphosphate; mesenteric vascular bed; rat