Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure

Int J Mol Med. 2014 Sep;34(3):756-64. doi: 10.3892/ijmm.2014.1829. Epub 2014 Jul 2.


It is known that apelin has definite protective effects on various cardiovascular diseases; however, the mechanism through which hypertension with heart failure (H-HF) is affected by pyroglutamylated apelin-13 (Pyr-AP13) remain unclear. Thus, in the present study, we investigated the effects of apelin on the cardiac hemodynamics in rats with hypertension and heart failure. In our study, cardiac function, dimensions and histological determination of the fibrosis of rats with two-kidney, one-clip induced hypertension and sham-operated rats were assessed using an echocardiography system and Masson's trichrome. The infusion of either 5% glucose injection (GS) alone or 5% GS containing Pyr-AP13 as a dose, time-matched design on the cardiac hemodynamics in H-HF rats and sham-operated rats was recorded. For the determination of the effects of potential related proteins on cardiac hemodynamics in the H-HF rats, the animals were divided into 5 groups: i) the sham-operated group (n=8); ii) H-HF (n=8); iii) H-HF with infusion of 0.1 µg dose of Pyr-AP13 (n=8) or 5% glucose (GS) (n=8); iv) H-HF with infusion of 1 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8); and v) H-HF with infusion of 10 µg dose of Pyr-AP13 (n=8) or 5% GS (n=8). The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) was determined by ELISA. The expression of membrane and cytosolic proteins was evaluated by western blot analysis. Significant cardiac and perivascular fibrosis was observed in the H-HF rats. Following the infusion of Pyr-AP13, the systolic and diastolic function was significantly improved in the cardiac hemodynamic parameters in the H-HF rats treated with Pyr-AP13. The apelin receptor (APJ), which was activated by the exogenous infusion of Pyr-AP13, was partially recycled from the cytoplasm back to the plasma membrane; however, membrane APJ was eventually downregulated in the H-HF rats treated with Pyr-AP13 compared with the sham-operated group rats. Our findings suggested that a complex was formed after Pyr-AP13 combined with cellular membrane APJ receptor. However, the endogenous downregulation of the APJ receptor results in benefits from the exogenous administration of apelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apelin Receptors
  • Cardiotonic Agents / pharmacology
  • Cell Separation
  • Cyclic AMP / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibrosis
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Failure / complications*
  • Heart Failure / physiopathology*
  • Hemodynamics / drug effects*
  • Hypertension / complications
  • Hypertension / diagnostic imaging
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / enzymology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / metabolism
  • Time Factors
  • Ultrasonography
  • Ventricular Function, Left / drug effects


  • Apelin Receptors
  • Aplnr protein, rat
  • Cardiotonic Agents
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide
  • Cyclic AMP
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases