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BioMed Research International
Volume 2018, Article ID 3293584, 9 pages
https://doi.org/10.1155/2018/3293584
Research Article

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

1Universities of Giessen and Marburg Lung Centre (UGMLC), Aulweg 130, 35392 Giessen, Germany
2German Center for Lung Research (DZL), 35392 Giessen, Germany
3Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
4Bayer Pharma AG, Aprather Weg 18a, 42096 Wuppertal, Germany
5Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany

Correspondence should be addressed to Ralph Theo Schermuly; ed.nesseig-inu.dem.erenni@ylumrehcs.hplar

Received 7 July 2017; Revised 4 November 2017; Accepted 16 November 2017; Published 3 January 2018

Academic Editor: Ruxandra Jurcut

Copyright © 2018 Nabham Rai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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, ), riociguat (30 mg/kg/d, ), or vehicle () 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.