Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Y1 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 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.
Zukowska-Grojec
Z
Z
Department of Physiology, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. zzukow01@gumedlib.dml.georgetown.edu
Dayao
E K
EK
Karwatowska-Prokopczuk
E
E
Hauser
G J
GJ
Doods
H N
HN
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D006439:Hemodynamics; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000502:physiology*
C092926:BIBP 3226; D017476:Receptors, Neuropeptide Y; D001120:Arginine