title: Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats.
abstract: OBJECTIVE
  The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats.
  
  
  METHODS
  Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated.
  
  
  RESULTS
  Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (± dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK.
  
  
  CONCLUSIONS
  This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.
authors: Department of Pharmacology, State-Province Key Laboratory of Biomedicine - Pharmaceutics of China, Harbin Medical University, Harbin, Heilongjiang, China.
authors: Rong
authors: R
authors: Zhang
authors: Huifang
authors: H
authors: Niu
authors: Xiaohui
authors: X
authors: Kang
authors: Tao
authors: T
authors: Ban
authors: Hong
authors: H
authors: Hong
authors: Jing
authors: J
authors: Ai
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism; D006984:Hypertrophy / Q000139:chemically induced* / Q000378:metabolism; D055104:Infusions, Subcutaneous / Q000379:methods; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D024723:Ventricular Myosins / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin; D024723:Ventricular Myosins