Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y-1 receptors

The physiological role of neuropeptide Y (NPY), a sympathetic cotransmitter and vasoconstrictor, has not been determined yet. We used a specific nonpeptide antagonist to the NPY Y-1 receptor {BIBP-3226; (R)-N-2-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl] -D-arginineamide} to study the involvement of NPY in stress-induced vasoconstriction in the mesenteric bed. In rats subjected to cold water stress (COLD), plasma NPY immunoreactivity levels increased progressively from 0.15 +/- 0.01 to 0.32 +/- 0.05 pmol/ml and remained elevated during recovery. Administration of BIBP-3226 (3 mg . kg(-1). h(-1) infusion) tended to decrease the stress-induced presser response and significantly attenuated the post-COLD elevation of blood pressure. The COLD-induced fall in the superior mesenteric artery blood flow and the increase of up to 300% in the mesenteric vascular resistance were either reduced or eliminated by BIBP-3226. Conversely, the Y-1 antagonist had no effect on the COLD-induced tachycardia. This study provides the first evidence of the physiological role of NPY. The peptide is released during stress and increases mesenteric vascular resistance via activation of its Y-1 receptors. Specific Y-1-receptor antagonists may therefore be of potential benefit in prevention or treatment of stress-induced vasospasm.