ArticlePloS one2011
Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 102 citations in OpenAlex.
- Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2.Annals of the rheumatic diseases · 2017Trial
- Soluble guanylate cyclase modulators-a novel therapeutic approach for diabetic kidney disease.Renal failure · 2025Review
- Riociguat Alleviates Cisplatin-Caused Kidney Injury by Suppressing Oxidative Stress and Inflammation.Biology · 2025Article
- Targeting the NO-sGC-cGMP Pathway: Mechanisms of Action of Vericiguat in Chronic Heart Failure.Cells · 2025Review
- Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome bMitochondrion · 2025Article
- Article
- Nephroprotective effects of the soluble guanylyl cyclase stimulator, riociguat in doxorubicin-induced acute kidney injury in rats.Toxicology reports · 2024Article
- Review
- Pharmacology and Emerging Therapies for Group 3 Pulmonary Hypertension Due to Chronic Lung Disease.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- Tissue Sodium Accumulation: Pathophysiology and Clinical Implications.Antioxidants (Basel, Switzerland) · 2022Review
- SGLT2 inhibition potentiates the cardiovascular, renal, and metabolic effects of sGC stimulation in hypertensive rats with prolonged exposure to high-fat diet.American journal of physiology. Heart and circulatory physiology · 2022Article
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- Newer Drugs to Reduce High Blood Pressure and Mitigate Hypertensive Target Organ Damage.Current hypertension reports · 2022Review
- Article
- 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
- Article
- Olinciguat, an Oral sGC Stimulator, Exhibits Diverse Pharmacology Across Preclinical Models of Cardiovascular, Metabolic, Renal, and Inflammatory Disease.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. METHODS AND
resultsMortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.
conclusionsStimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.
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Registered trials
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