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 Y2 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 10 μg/kg day (IA infusion, 14 days) of either PYY or PYY3–36 and did not differ from that obtained with a maximally angiogenic dose of VEGF165. Pharmacodynamic modeling based upon single dose pharmacokinetic plasma profiles of both agonists suggests that Emax is reached when the Y2 receptor is occupied by ≥50%. Furthermore, for PYY3–36, occupancy of the Y2 receptor is sufficient to promote a significant benefit in collateral blood flow.