TY - JOUR T1 - Induction of Hypertrophic Responsiveness of Cardiomyocytes to Neuropeptide Y in Response to Pressure Overload JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 581 LP - 591 DO - 10.1124/jpet.102.038448 VL - 303 IS - 2 AU - David Bell AU - Adrian R. Allen AU - Elizabeth J. Kelso AU - Ambikaipakan Balasubramaniam AU - Barbara J. McDermott Y1 - 2002/11/01 UR - http://jpet.aspetjournals.org/content/303/2/581.abstract N2 - To determine whether neuropeptide Y (NPY)-related mechanisms become activated with progression of cardiac hypertrophy in vivo, protein mass and de novo protein synthesis (incorporation of [14C]Phe, 0.1 μCi ml−1) were assessed in cardiomyocytes, obtained from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (8, 12, 16, 20, and 24 weeks of age), and cultured for 24 h. NPY (10−8 M) increased protein mass of cardiomyocytes from 16-week-old SHRs by 9.2 ± 2.1% (n = 8, P < 0.05). De novo protein synthesis was increased maximally in SHRs at 12, 16, and 20 weeks (P < 0.05, n = 8) in response to NPY by 12.6 ± 2.1% (10−6 M), 20.1 ± 4.2% (10−8 M), and 9.4 ± 1.8% (10−7 M), respectively. Peptide YY3–36, (PYY3–36), which displays selectivity for NPY Y2 and NPY Y5 receptors, and the NPY Y5-selective agonist [d-Trp34]-NPY increased de novo protein synthesis maximally by 16.2 ± 5.1% (10−7 M;n = 4, P < 0.05) and 17.8 ± 5.2% (10−6 M; n = 7,P < 0.05), respectively, in SHRs at 16 weeks, whereas [Leu31Pro34]-NPY (≤10−6 M), which displays some activity at NPY Y1 and NPY Y4 receptors, did not. The NPY Y1-selective antagonist BVD-42 (2 × 10−7M) and the NPY Y2-selective antagonist BIIE0246 (2 × 10−7 M) did not attenuate responses to NPY (10−7 M) and PPY3–36 (10−7 M). These data indicate that hypertrophic responsiveness to NPY, mediated via NPY Y5 receptors, is induced transiently in SHR cardiomyocytes subsequent to onset of cardiomyocyte hypertrophy in response to pressure overload. The American Society for Pharmacology and Experimental Therapeutics ER -