ArticlePloS one2012
The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03362047 (Untersuchung Des Einflusses PAH-spezifischer Medikation Auf Die rechtsventrikuläre Funktion Bei Patienten Mit Pulmonaler Arterieller Hypertonie), which is not on this map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Untersuchung Des Einflusses PAH-spezifischer Medikation Auf Die rechtsventrikuläre Funktion Bei Patienten Mit Pulmonaler Arterieller Hypertonie (PAH) Unter Basalen Bedingungen
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pooled it
- Effects of riociguat on right ventricular size and function in pulmonary arterial hypertension (RIVER II): a prospective, phase IV study.Respiratory research · 2026Trial
- A multicenter randomized, double-blind, placebo-controlled pilot study to assess the efficacy and safety of riociguat in systemic sclerosis-associated digital ulcers.Arthritis research & therapy · 2019Trial
- Right ventricular size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (the RIVER study).Respiratory research · 2018Trial
- The Therapeutic Efficacy of Drugs Targeting the NO-sGC-cGMP Pathway in Treatment of Patients With Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review.Pulmonary circulation · 2026Review
- Contemporary treatment of right ventricular failure.JHLT open · 2025Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Analysis of riociguat and desmethyl riociguat by UPLC-MS/MS and its interaction with quercetin.Frontiers in pharmacology · 2024Article
- Exploring the pathogenesis of pulmonary vascular disease.Frontiers in medicine · 2024Review
- Right ventricular failure in pulmonary hypertension: recent insights from experimental models.Herz · 2023Review
- Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model.Frontiers in pharmacology · 2023Article
- β3 adrenergic agonism: A novel pathway which improves right ventricular-pulmonary arterial hemodynamics in pulmonary arterial hypertension.Physiological reports · 2023Article
- Drug repurposing-a promising approach for patients with angina but non-obstructive coronary artery disease (ANOCA).Frontiers in cardiovascular medicine · 2023Review
- Riociguat and the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.European respiratory review : an official journal of the European Respiratory Society · 2022Review
- Novel use of riociguat in infants with severe pulmonary arterial hypertension unable to wean from inhaled nitric oxide.Frontiers in pediatrics · 2022Article
- Bibliometric study of soluble guanylate cyclase stimulators in cardiovascular research based on web of science from 1992 to 2021.Frontiers in pharmacology · 2022Article
- Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2021Article
- Riociguat: Clinical research and evolving role in therapy.British journal of clinical pharmacology · 2021Review
- Soluble Guanylate Cyclase Stimulators and Activators.Handbook of experimental pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signal-transduction pathway is impaired in many cardiovascular diseases, including pulmonary arterial hypertension (PAH). Riociguat (BAY 63-2521) is a stimulator of sGC that works both in synergy with and independently of NO to increase levels of cGMP. The aims of this study were to investigate the role of NO-sGC-cGMP signaling in a model of severe PAH and to evaluate the effects of sGC stimulation by riociguat and PDE5 inhibition by sildenafil on pulmonary hemodynamics and vascular remodeling in severe experimental PAH. METHODS AND
resultsSevere 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).
conclusionRiociguat and sildenafil significantly reduced RVSP and RVH, and improved RV function compared with vehicle. Riociguat had a greater effect on hemodynamics and RVH than sildenafil.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.