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The Y2 receptor mediates increases in collateral-dependent blood flow in a model of peripheral arterial insufficiency
Charles A Cruze1, Frank Su, Brian J Limberg
1Procter & Gamble Pharmaceuticals, Mason Business Center, 8700 Mason-Montgomery Road, Mason, OH 45040-9317, USA.
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.
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