Abstract | BACKGROUND: METHODS AND RESULTS: Severe angioproliferative PAH was induced in rats by combined exposure to the vascular endothelial growth factor receptor antagonist SU5416 and hypoxia (SUHx). Twenty-one days thereafter rats were randomized to receive either riociguat (10 mg/kg/day), sildenafil (50 mg/kg/day) or vehicle by oral gavage, for 14 days until the day of the terminal hemodynamic measurements. Administration of riociguat or sildenafil significantly decreased right ventricular systolic pressure (RVSP). Riociguat significantly decreased RV hypertrophy (RVH) (0.55 ± 0.02, p<0.05), increased cardiac output (60.8 ± .8 mL/minute, p<0.05) and decreased total pulmonary resistance (4.03 ± 0.3 mmHg min(-1) ml(-1) 100 g BW, p<0.05), compared with sildenafil and vehicle. Both compounds significantly decreased the RV collagen content and improved RV function, but the effects of riociguat on tricuspid annular plane systolic excursion and RV myocardial performance were significantly better than those of sildenafil (p<0.05). The proportion of occluded arteries was significantly lower in animals receiving riociguat than in those receiving vehicle (p<0.05); furthermore, the neointima/media ratio was significantly lower in those receiving riociguat than in those receiving sildenafil or vehicle (p<0.05). CONCLUSION:
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Authors | Michaela Lang, Baktybek Kojonazarov, Xia Tian, Anuar Kalymbetov, Norbert Weissmann, Friedrich Grimminger, Axel Kretschmer, Johannes-Peter Stasch, Werner Seeger, Hossein Ardeschir Ghofrani, Ralph Theo Schermuly |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 8
Pg. e43433
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22912874
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Indoles
- Phosphodiesterase 5 Inhibitors
- Piperazines
- Purines
- Pyrazoles
- Pyrimidines
- Pyrroles
- Receptors, Cytoplasmic and Nuclear
- Sulfones
- Semaxinib
- Sildenafil Citrate
- Nitric Oxide Synthase Type III
- Caspase 3
- Guanylate Cyclase
- Soluble Guanylyl Cyclase
- Cyclic GMP
- riociguat
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Topics |
- Animals
- Apoptosis
(drug effects)
- Blood Pressure
(drug effects)
- Blotting, Western
- Caspase 3
(metabolism)
- Cell Proliferation
(drug effects)
- Cyclic GMP
(metabolism)
- Guanylate Cyclase
(metabolism)
- Hemodynamics
(drug effects)
- Hypertension, Pulmonary
(etiology, physiopathology, prevention & control)
- Hypertrophy, Right Ventricular
(physiopathology, prevention & control)
- Hypoxia
(complications)
- Immunohistochemistry
- Indoles
(toxicity)
- Lung
(drug effects, metabolism, physiopathology)
- Male
- Nitric Oxide Synthase Type III
(metabolism)
- Phosphodiesterase 5 Inhibitors
(pharmacology)
- Piperazines
(pharmacology)
- Purines
(pharmacology)
- Pyrazoles
(pharmacology)
- Pyrimidines
(pharmacology)
- Pyrroles
(toxicity)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Receptors, Cytoplasmic and Nuclear
(metabolism)
- Sildenafil Citrate
- Soluble Guanylyl Cyclase
- Sulfones
(pharmacology)
- Time Factors
- Treatment Outcome
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