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Effects of riociguat in severe experimental pulmonary hypertension

  • Baktybek Kojonazarov1Email author,
  • Michaela Lang1,
  • Norbert Weissmann1,
  • Friedrich Grimminger1,
  • Johannes-Peter Stasch2,
  • Werner Seeger1, 3,
  • Hossein Ardeschir Ghofrani1 and
  • Ralph Schermuly1, 3
BMC Pharmacology201111(Suppl 1):P39

Published: 1 August 2011


Pulmonary HypertensionPDE5 InhibitorMyocardial Performance IndexSoluble Guanylate CyclaseRight Ventricular Systolic Pressure


The NO-sGC-cGMP signaling pathway is impaired in different cardiovascular diseases, including pulmonary hypertension (PH). Riociguat is the first of a new class of drugs, the soluble guanylate cyclase stimulators. Riociguat has a dual mode of action: it sensitizes sGC to the body’s own NO and can also increase sGC activity in the absence of NO, causing vasorelaxation, anti-proliferation and anti-fibrotic effects.

The aim of the study was to investigate the effects of riociguat as compared to the PDE5 inhibitor sildenafil on pulmonary vascular remodeling in severe experimental PH.


Angioproliferative PH was induced in rats by combined exposure to the vascular endothelial growth factor-receptor antagonist SU5416 and hypoxia at 10%O2 (SU+HOX). Twenty-one days thereafter, rats were randomized for treatment with riociguat (10 mg/kg), sildenafil (50 mg/kg) or vehicle for the next 14 days. Echocardiography and invasive hemodynamic measurements were performed. Pulmonary vascular remodeling was assessed by histomorphometric analysis.


In rats with established PH, right ventricular systolic pressure (RVSP) was significantly decreased by treatment with riociguat to 73±4 mmHg (p<0.01) and sildenafil to 80±3 mmHg (p<0.05) as compared to placebo (89±3 mmHg). No significant difference in systemic arterial pressure was detected between placebo and treated animals. Both compounds significantly decreased RV hypertrophy and improved RV function by normalization of TAPSE and myocardial performance index, but effects of riociguat were more pronounced. Riociguat significantly reduced the proportion of occluded arteries and increased proportion of opened arteries and decreased neointima/media ratio.


We demonstrated that riociguat effectively suppresses pulmonary vascular remodeling and significantly improves RV function in an experimental model of severe PH.

Authors’ Affiliations

University of Giessen Lung Center, Giessen, Germany
Bayer HealthCare, Wuppertal, Germany
Department of Lung Development and Remodeling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany


© Kojonazarov et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.