The Y 2 receptor mediates increases in collateral-dependent blood flow in a model of peripheral arterial insufficiency

• Published in: Peptides (New York, N.Y. : 1980) Vol. 28; no. 2; pp. 269 - 280
• Main Authors: Cruze, Charles A., Su, Frank, Limberg, Brian J., Deutsch, Angela J., Stoffolano, Peter J., Dai, H. Jian, Buchanan, Danielle D., Yang, H.T., Terjung, Ronald L., Spruell, Russell D., Mittelstadt, Scott W., Rosenbaum, Jan S.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.02.2007
• Subjects: Angiogenesis; Arteriogenesis; Collateral blood flow; Intermittent claudication; NPY; Peripheral arterial disease (PAD); PYY; PYY 3–36; Therapeutic angiogenesis; Vascular remodeling; Y 2 receptor; Peripheral arterial disease (PAD); NO; FGF; IBMX; Intermittent claudication; S.D; PYY 3–36; EDTA; cAMP; S.E.M; Vascular remodeling; PYY; DMEM; BSA; Angiogenesis; Arteriogenesis; PAD; NPY; HEPES; VEGF 165; Therapeutic angiogenesis; Y 2 receptor; Collateral blood flow
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2006.09.026

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.