Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

Cell Physiol Biochem. 2015;37(1):94-104. doi: 10.1159/000430336. Epub 2015 Aug 17.

Abstract

Background/aims: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Calcineurin / metabolism
  • Heart / drug effects*
  • Heart Diseases / chemically induced*
  • Heart Diseases / metabolism
  • Hypertrophy / chemically induced*
  • Hypertrophy / metabolism
  • Infusions, Subcutaneous / methods
  • Male
  • Neuropeptide Y / administration & dosage*
  • Neuropeptide Y / adverse effects*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Ventricular Function, Left / drug effects*
  • Ventricular Myosins / metabolism
  • Ventricular Remodeling / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Neuropeptide Y
  • p38 Mitogen-Activated Protein Kinases
  • Calcineurin
  • Ventricular Myosins