The Y1 antagonist BIBP 3226 inhibits potentiation of methoxamine-induced vasoconstriction by neuropeptide Y.
We investigated the interaction of neuropeptide Y (NPY) with the alpha 1-adrenoceptor agonist, methoxamine, in control of mean arterial pressure, renovascular resistance and mesenteric vascular resistance in anaesthetized rats. Infusion of 3.0 but not 0.3 microgram/kg/min NPY enhanced the elevations of all three haemodynamic parameters caused by bolus injections of methoxamine (10-100 micrograms/kg). These enhancements largely involved a prolongation of the methoxamine effects. While infusion of the Y1 NPY receptor-selective antagonist, BIBP 3226 (10 micrograms/kg/min), alone did not alter methoxamine-induced vasoconstriction, it inhibited the potentiation by NPY. We conclude that NPY can potentiate methoxamine-induced vasoconstriction in vivo. This is mediated predominantly, if not exclusively, via the Y1 receptor. Endogenously released NPY does not appear to reach sufficient concentrations to cause tonic systemic vasoconstriction or potentiation thereof in the anaesthetized rat.
Bischoff
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Nephrol. Lab. IG 1, Klinikum, Essen, Germany.
Freund
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Michel
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000037:antagonists & inhibitors*; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; D001120:Arginine; D008729:Methoxamine