Postinfarct treatment with oxytocin improves cardiac function and remodeling via activating cell-survival signals and angiogenesis

J Cardiovasc Pharmacol. 2009 Dec;54(6):510-9. doi: 10.1097/FJC.0b013e3181bfac02.

Abstract

Background: We investigated whether postinfarct treatment with oxytocin (OT) improves left ventricular (LV) function and remodeling via cardiac repair of myocardial ischemia-reperfusion injury.

Methods and results: Experiments were performed with 30 minutes of coronary occlusion and 2 or 14 days of reperfusion rabbit model of myocardial infarction. LV function and remodeling were significantly improved in the OT group. The infarct size was significantly reduced in the OT group. The number of CD31-positive microvessels was increased significantly in the OT group. There were no Ki67-positive myocytes in either group. The expression of the OT receptor, phosphorylated (p)-Akt protein kinase, p-extracellular signal-regulated protein kinase, p-enodthelial NO synthase, p-signal transducer and activator of transcription 3, vascular endothelial growth factor, B-cell lymphoma 2, and matrix metalloproteinase-1 (MMP-1) were markedly increased in the OT group days 2 and 14 post myocardial infarction.

Conclusions: Postinfarct treatment with OT reduces myocardial infarct size and improves LV function and remodeling by activating OT receptors and prosurvival signals and by exerting antifibrotic and angiogenic effects through activation of MMP-1, endothelial NO synthase, and vascular endothelial growth factor. These findings provide new insight into therapeutic strategies for ischemic heart disease.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cyclin D1 / metabolism
  • Disease Models, Animal
  • Echocardiography
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Heart / drug effects
  • Heart / physiopathology
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Male
  • Matrix Metalloproteinase 1 / metabolism
  • Microvessels / anatomy & histology
  • Microvessels / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Neovascularization, Physiologic / drug effects*
  • Nitric Oxide Synthase Type III / metabolism
  • Oxytocin / pharmacology
  • Oxytocin / therapeutic use*
  • Phosphorylation / drug effects
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rabbits
  • Receptors, Oxytocin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Stroke Volume / drug effects
  • Stroke Volume / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / physiology
  • Ventricular Remodeling / drug effects*
  • Ventricular Remodeling / physiology

Substances

  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Oxytocin
  • STAT3 Transcription Factor
  • Vascular Endothelial Growth Factor A
  • Cyclin D1
  • Oxytocin
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 1