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 ∼60% (p<0.001) was obtained with a 10μg/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 ≥50%. Furthermore, for PYY 3–36 , occupancy of the Y 2 receptor is sufficient to promote a significant benefit in collateral blood flow.