The neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226: equal effects on vascular responses to exogenous and endogenous NPY in the pig in vivo

British Journal of Pharmacology
R E MalmströmJ M Lundberg

Abstract

1. The antagonistic effects of the neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 on equally prominent vascular responses evoked by sympathetic nerve stimulation and exogenous NPY were compared during different intravenous (i.v.) infusions of the antagonist (0.19-190 nmol kg-1 min-1 for 30 min). 2. High frequency sympathetic nerve stimulation in reserpine-treated pigs in vivo evoked non-adrenergic vasoconstrictor responses in kidney and hind limb, in the latter followed by a long-lasting phase of decreased blood flow. The vascular response in the kidney and the long-lasting phase in hind limb resembled the effects of exogenous NPY administered i.v. (kidney) and intraarterially (i.a.) (in the hind limb, which only responded to higher NPY doses). 3. Plasma levels of BIBP 3226 reached a plateau within 20 min and the inhibitory effects on vascular responses were studied during the last ten minutes of infusion. The elimination of BIBP 3226 from plasma was found to fit a two-compartment model with an alpha-phase of 2.0 +/- 0.2 min and a beta-phase of 20.1 +/- 0.9 min. 4. Significant inhibition of presumably Y1 receptor-mediated vascular responses evoked by both endogenous and exogenous NPY in kidney and hind limb was seen even...Continue Reading

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Citations

Jan 25, 2012·Cellular and Molecular Neurobiology·Dalay Hirsch, Zofia Zukowska
May 4, 2001·European Journal of Pharmacology·R E MalmströmM Sjölander
Jul 11, 2002·European Journal of Pharmacology·Rickard E Malmström
Apr 4, 1998·European Journal of Pharmacology·S P DucklesD N Krause
Dec 8, 2000·Autonomic Neuroscience : Basic & Clinical·M J McCloskey, E K Potter
Mar 22, 2000·British Journal of Pharmacology·Y DumontR Quirion
Jun 12, 2004·Clinical and Experimental Pharmacology & Physiology·Gabriela A EppelRoger G Evans
Jul 6, 2004·Autonomic Neuroscience : Basic & Clinical·Gabriela A EppelRoger G Evans
Oct 12, 2000·Journal of Cardiovascular Pharmacology·R E MalmströmJ Weilitz

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