ReviewCurrent heart failure reports2012
Recoupling the cardiac nitric oxide synthases: tetrahydrobiopterin synthesis and recycling.
Review in Current heart failure reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 133 citations in OpenAlex.
- No QTcF Prolongation with Sepiapterin: Results From a Thorough QT Study in Healthy Subjects at Therapeutic and Supratherapeutic Doses.Journal of clinical pharmacology · 2026Trial
- Impaired systemic tetrahydrobiopterin bioavailability and increased oxidized biopterins in pediatric falciparum malaria: association with disease severity.PLoS pathogens · 2015Trial
- Regional myosin mechanosensing dysfunction under metabolic stress.The Journal of physiology · 2026Article
- The Metabolic Architecture of Glaucoma: A Unified Framework of Cofactor Failure and Kynurenine Dysregulation.International journal of molecular sciences · 2026Review
- Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control.Redox biology · 2026Review
- Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers.International journal of molecular sciences · 2026Review
- Mapping the Nitric Oxide Axis in IVF: Genotype Associations in Antagonist Cycles.International journal of molecular sciences · 2025Article
- Morphometric and Molecular Interplay in Hypertension-Induced Cardiac Remodeling with an Emphasis on the Potential Therapeutic Implications.International journal of molecular sciences · 2025Review
- L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.Nutrients · 2025Review
- Declining nitric oxide bioavailability in cardiovascular aging: mechanistic insights and emerging interventions.The journal of cardiovascular aging · 2025Article
- Inhibition of Ferroptosis by Mesenchymal Stem Cell-Derived Exosomes in Acute Spinal Cord Injury: Role of Nrf2/GCH1/BH4 Axis.Neurospine · 2024Article
- Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection.Antioxidants (Basel, Switzerland) · 2024Review
- ROS-Induced Endothelial Dysfunction in the Pathogenesis of Atherosclerosis.Aging and disease · 2024Review
- Reactive oxygen species (ROS)-responsive biomaterials for treating myocardial ischemia-reperfusion injury.Frontiers in bioengineering and biotechnology · 2024Review
- Abscisic Acid and Its Receptors LANCL1 and LANCL2 Control Cardiomyocyte Mitochondrial Function, Expression of Contractile, Cytoskeletal and Ion Channel Proteins and Cell Proliferation via ERRα.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- Protective effect of IAXO-102 on renal ischemia-reperfusion injury in rats.Journal of medicine and life · 2023Article
- Serum folic acid: an effective indicator for arteriogenic erectile dysfunction.Frontiers in endocrinology · 2023Article
- Revitalizing cardiac health in chronic renal failure: the synergistic effects of angiotensin-converting enzyme inhibitors and vitamin C in modulating nitric oxide and left ventricular hypertrophy.Archives of medical sciences. Atherosclerotic diseases · 2023Article
- Uncoupled nitric oxide synthase activity promotes colorectal cancer progression.Frontiers in oncology · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO), a key regulator of cardiovascular function, is synthesized from L-arginine and oxygen by the enzyme nitric oxide synthase (NOS). This reaction requires tetrahydrobiopterin (BH4) as a cofactor. BH4 is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GTPCH) and recycled from 7,8-dihydrobiopterin (BH2) by dihydrofolate reductase. Under conditions of low BH4 bioavailability relative to NOS or BH2, oxygen activation is "uncoupled" from L-arginine oxidation, and NOS produces superoxide (O (2) (-) ) instead of NO. NOS-derived superoxide reacts with NO to produce peroxynitrite (ONOO(-)), a highly reactive anion that rapidly oxidizes BH4 and propagates NOS uncoupling. BH4 depletion and NOS uncoupling contribute to overload-induced heart failure, hypertension, ischemia/reperfusion injury, and atrial fibrillation. L-arginine depletion, methylarginine accumulation, and S-glutathionylation of NOS also promote uncoupling. Recoupling NOS is a promising approach to treating myocardial and vascular dysfunction associated with heart failure.
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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.