Science and Research

Effect of Riociguat and Sildenafil on Right Heart Remodeling and Function in Pressure Overload Induced Model of Pulmonary Arterial Banding

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and a rise in right ventricular (RV) afterload. The increased RV afterload leads to right ventricular failure (RVF) which is the reason for the high morbidity and mortality in PAH patients. The objective was to evaluate the therapeutic efficacy and antiremodeling potential of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the soluble guanylate cyclase stimulator riociguat in a model of pressure overload RV hypertrophy induced by pulmonary artery banding (PAB). Mice subjected to PAB, one week after surgery, were treated with either sildenafil (100 mg/kg/d, n = 5), riociguat (30 mg/kg/d, n = 5), or vehicle (n = 5) for 14 days. RV function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometry. Both sildenafil and riociguat prevented the deterioration of RV function, as determined by a decrease in RV dilation and restoration of the RV ejection fraction (EF). Although both compounds did not decrease right heart mass and cellular hypertrophy, riociguat prevented RV fibrosis induced by PAB. Both compounds diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Treatment with either riociguat or sildenafil prevented the progression of pressure overload-induced RVF, representing a novel therapeutic approach.

  • Rai, N.
  • Veeroju, S.
  • Schymura, Y.
  • Janssen, W.
  • Wietelmann, A.
  • Kojonazarov, B.
  • Weissmann, N.
  • Stasch, J. P.
  • Ghofrani, H. A.
  • Seeger, W.
  • Schermuly, R. T.
  • Novoyatleva, T.

Keywords

  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 5/genetics
  • Disease Models, Animal
  • Heart/drug effects/physiopathology
  • Heart Failure/*drug therapy/genetics/pathology
  • Heart Ventricles/drug effects/physiopathology
  • Humans
  • Hypertension, Pulmonary/*drug therapy/genetics/pathology
  • Male
  • Mice
  • Phosphodiesterase 5 Inhibitors/administration & dosage
  • Pressure
  • Pulmonary Artery/drug effects/physiopathology
  • Pyrazoles/*administration & dosage
  • Pyrimidines/*administration & dosage
  • Sildenafil Citrate/*administration & dosage
  • Vascular Remodeling/drug effects
  • Ventricular Dysfunction, Right/*drug therapy/genetics/pathology
Publication details
DOI: 10.1155/2018/3293584
Journal: BioMed research international
Pages: 3293584 
Work Type: Original
Location: UGMLC
Disease Area: PH
Partner / Member: JLU, MPI-BN
Access-Number: 29511676
See publication on PubMed

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