Therapeutic effects of continuous infusion of brain natriuretic peptides on postmyocardial infarction ventricular remodelling in rats

Arch Cardiovasc Dis. 2011 Jan;104(1):17-28. doi: 10.1016/j.acvd.2010.09.006. Epub 2010 Dec 17.


Background: Previous studies have shown protective effects of brain natriuretic peptide (BNP) against the postmyocardial infarction (MI) remodelling process. The transcription factor NF-κB is known to play an important role after MI.

Aims: To investigate if NF-κB is involved in the protective effects of BNP against adverse post-MI remodelling.

Methods: Rats were randomly assigned to five groups: sham-operation; MI by coronary ligation; MI treated with chronic BNP infusion; MI treated with enalapril; MI treated with BNP+enalapril. Rats were closely monitored for survival rate analysis. Rats from each group were sacrificed on days 3, 7 and 28 postoperation.

Results: The results showed that chronic continuous BNP infusion achieved similar effects to enalapril therapy, as evidenced by improved survival rate within the 28-day observation period compared with MI group rats; this effect was closely associated with preserved cardiac geometry and performance. The treatment combination did not offer extra benefits in terms of survival rate. Both BNP and enalapril therapy produced higher heart tissue concentrations of cyclic guanosine monophosphate and lower expression levels of inflammatory cytokines, including tumour necrosis factor-α, interleukin-1 and interleukin-6. These benefits were associated with lower phosphorylation levels of NF-κB subunits IκBα, p50 and p65. While enalapril significantly inhibited extracellular matrix remodelling via regulation of the protein expression ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinase and the activity of matrix metalloproteinase, these variables were not affected by BNP, indicating that the two therapies involve different mechanisms.

Conclusion: Chronic BNP infusion can provide beneficial effects against adverse post-MI remodelling.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Cardiovascular Agents / administration & dosage*
  • Collagen / metabolism
  • Cyclic GMP / metabolism
  • Disease Models, Animal
  • Enalapril / pharmacology
  • Hemodynamics
  • I-kappa B Proteins / metabolism
  • Inflammation Mediators / metabolism
  • Infusion Pumps, Implantable
  • Infusions, Intravenous
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B p50 Subunit / metabolism
  • Natriuretic Peptide, Brain / administration & dosage*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transcription Factor RelA / metabolism
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • I-kappa B Proteins
  • Inflammation Mediators
  • NF-kappa B p50 Subunit
  • Nfkbia protein, rat
  • Rela protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Transcription Factor RelA
  • Angiotensin II
  • Natriuretic Peptide, Brain
  • NF-KappaB Inhibitor alpha
  • Enalapril
  • Collagen
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Cyclic GMP