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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 ∼60% ( p < 0.001) was obtained with a 10 μg/kg day (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.
Published Version
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