Comparative evaluation of torasemide and spironolactone on adverse cardiac remodeling in a rat model of dilated cardiomyopathy

Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12283.

Abstract

Background: Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion.

Methods: To identify the effects of diuretic agents on adverse cardiac remodeling in CHF, this study was carried out, where we have compared the effects of torasemide and spironolactone in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin-mediated experimental autoimmune myocarditis.

Results: Cardiac protein expression levels of inflammation, endoplasmic reticulum stress, and fibrosis markers were upregulated in the hearts of CHF rats, while treatment with either torasemide or spironolactone has downregulated their expression. The effect produced by spironolactone on cardiac fibrosis markers was comparably lesser than torasemide. Further, immunohistochemical analysis and histopathological studies have provided evidence to confirm the beneficial effects of these drugs on adverse cardiac remodeling in rats with CHF.

Conclusion: Torasemide treatment has benefits against adverse cardiac remodeling in CHF rats, which was better than the protection offered by spironolactone.

Keywords: Adverse remodeling; Cardiac fibrosis; Collagen; ER stress.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Autoimmunity
  • Biomarkers / metabolism
  • Cardiac Myosins
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / etiology
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / physiopathology
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects
  • Fibrosis
  • Heart Ventricles / drug effects*
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Male
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Myocarditis / chemically induced
  • Myocarditis / immunology
  • Rats, Inbred Lew
  • Sodium Potassium Chloride Symporter Inhibitors / pharmacology*
  • Spironolactone / pharmacology*
  • Sulfonamides / pharmacology*
  • Torsemide
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Biomarkers
  • Mineralocorticoid Receptor Antagonists
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sulfonamides
  • Spironolactone
  • Cardiac Myosins
  • Torsemide