title: The Y2 receptor mediates increases in collateral-dependent blood flow in a model of peripheral arterial insufficiency.
abstract: We have utilized a rat model of peripheral artery disease (PAD) to examine whether the known angiogenic activity of the Y(2) receptor would translate into a meaningful increase in collateral blood flow. The maximal increase in collateral blood flow capacity of approximately 60% (p<0.001) was obtained with a 10microg/kgday (IA infusion, 14 days) of either PYY or PYY(3-36) and did not differ from that obtained with a maximally angiogenic dose of VEGF(165). Pharmacodynamic modeling based upon single dose pharmacokinetic plasma profiles of both agonists suggests that E(max) is reached when the Y(2) receptor is occupied by >or=50%. Furthermore, for PYY(3-36), occupancy of the Y(2) receptor is sufficient to promote a significant benefit in collateral blood flow.
authors.affiliation: Procter & Gamble Pharmaceuticals, Mason Business Center, 8700 Mason-Montgomery Road, Mason, OH 45040-9317, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Cruze
authors.forename: Frank
authors.initials: F
authors.lastname: Su
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Limberg
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Deutsch
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stoffolano
authors.forename: H Jian
authors.initials: HJ
authors.lastname: Dai
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: H T
authors.initials: HT
authors.lastname: Yang
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Terjung
authors.forename: Russell D
authors.initials: RD
authors.lastname: Spruell
authors.forename: Scott W
authors.initials: SW
authors.lastname: Mittelstadt
authors.forename: Jan S
authors.initials: JS
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D001483:Base Sequence; D001775:Blood Circulation / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D006801:Humans; D008954:Models, Biological; D016491:Peripheral Vascular Diseases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor