TY - JOUR T1 - Effects of riociguat in severe experimental pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 411 AU - Baktybek Kojonazarov AU - Michaela Lang AU - Norbert Weissmann AU - Friedrich Grimminger AU - Johannes-Peter Stasch AU - Werner Seeger AU - Hossein Ardeschir Ghofrani AU - Ralph Schermuly Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/411.abstract N2 - Introduction: 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 sGC 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.Aim: 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.Methods: Angioproliferative PH was induced in rats by combined exposure to the VEGFr antagonist SU5416 and hypoxia. 21 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 histomorphomety.Results: In rats with established PH, 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 Tei index, but effects of riociguat were more pronounced. Riociguat significantly reduced the proportion of occluded arteries, increased proportion of opened arteries and decreased neointima/media ratio.Conclusion: We demonstrated that riociguat effectively suppresses pulmonary vascular remodeling and significantly improves RV function in an experimental model of PH. ER -