Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy

Biofactors. 2017 Mar;43(2):187-194. doi: 10.1002/biof.1332. Epub 2016 Sep 24.

Abstract

Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell-cell interaction in the heart. © 2016 BioFactors, 43(2):187-194, 2017.

Keywords: cardiac fibrosis; connexin-43; furosemide; gap junction; torasemide.

MeSH terms

  • Animals
  • Cadherins / biosynthesis
  • Cardiac Myosins / adverse effects
  • Cardiomyopathy, Dilated / chemically induced
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / pathology
  • Connexin 43 / biosynthesis
  • Connexins / metabolism*
  • Disease Models, Animal
  • Furosemide / administration & dosage*
  • Gene Expression Regulation / drug effects
  • Heart Failure / chemically induced
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Humans
  • Rats
  • Sulfonamides / administration & dosage*
  • Swine
  • Torsemide

Substances

  • Cadherins
  • Connexin 43
  • Connexins
  • Sulfonamides
  • Furosemide
  • Cardiac Myosins
  • Torsemide