The Y2 receptor mediates increases in collateral-dependent blood flow in a model of peripheral arterial insufficiency.
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.
Cruze
Charles A
CA
Procter & Gamble Pharmaceuticals, Mason Business Center, 8700 Mason-Montgomery Road, Mason, OH 45040-9317, USA.
Su
Frank
F
Limberg
Brian J
BJ
Deutsch
Angela J
AJ
Stoffolano
Peter J
PJ
Dai
H Jian
HJ
Buchanan
Danielle D
DD
Yang
H T
HT
Terjung
Ronald L
RL
Spruell
Russell D
RD
Mittelstadt
Scott W
SW
Rosenbaum
Jan S
JS
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
D017931:DNA Primers; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor