Zukowska-Grojec Z, Dayao E K, Karwatowska-Prokopczuk E, Hauser G J, Doods H N
Department of Physiology, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H796-800. doi: 10.1152/ajpheart.1996.270.2.H796.
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 Y1 receptor [BIBP-3226; (R)-N2-(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 pressor 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 Y1 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 Y1 receptors. Specific Y1-receptor antagonists may therefore be of potential benefit in prevention or treatment of stress-induced vasospasm.
神经肽Y（NPY）作为一种交感神经共递质和血管收缩剂，其生理作用尚未明确。我们使用了一种针对NPY Y1受体的特异性非肽拮抗剂[BIBP - 3226；（R）-N2 -（二苯乙酰基）-N - [（4 - 羟苯基）甲基]-D - 精氨酸酰胺]来研究NPY在应激诱导的肠系膜床血管收缩中的作用。在遭受冷水应激（COLD）的大鼠中，血浆NPY免疫反应性水平从0.15±0.01逐渐升高至0.32±0.05 pmol/ml，并在恢复过程中保持升高。给予BIBP - 3226（3 mg·kg-1·h-1输注）倾向于降低应激诱导的升压反应，并显著减弱冷应激后血压的升高。BIBP - 3226可减轻或消除冷应激诱导的肠系膜上动脉血流量下降以及肠系膜血管阻力高达300%的增加。相反，Y1拮抗剂对冷应激诱导的心动过速没有影响。本研究首次提供了NPY生理作用的证据。该肽在应激期间释放，并通过激活其Y1受体增加肠系膜血管阻力。因此，特异性Y1受体拮抗剂在预防或治疗应激诱导的血管痉挛方面可能具有潜在益处。
