Long-term administration of neuropeptide y in the subcutaneous infusion results in cardiac dysfunction and hypertrophy in rats

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+/CaMdependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.