ArticleCardiovascular research2011
Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiology.
Article in Cardiovascular research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
- Oxidative Stress Biomarkers and Incidence of Postoperative Atrial Fibrillation in the Omega-3 Fatty Acids for Prevention of Postoperative Atrial Fibrillation (OPERA) Trial.Journal of the American Heart Association · 2015Trial
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- GCN5L1-Mediated Lysine Acetylation Regulates Mitochondrial Bioenergetics and Redox Homeostasis in the Aged Heart.Antioxidants (Basel, Switzerland) · 2026Article
- The correlation between Fischer's ratio and the risk of cardiac dysfunction in heart failure patients.BMC cardiovascular disorders · 2024Article
- Tyrosine to threonine ratio was related to heart failure with reduced or mildly reduced ejection fraction.ESC heart failure · 2024Article
- The value of phenylalanine in predicting atrial fibrillation risk in chronic heart failure.Frontiers in cardiovascular medicine · 2024Article
- High-fat stimulation induces atrial neural remodeling by reducing NO production via the CRIF1/eNOS/P21 axi.Lipids in health and disease · 2023Article
- Article
- Discrimination of serum metabolomics profiles in infants with sepsis, based on liquid chromatography-mass spectrometer.BMC infectious diseases · 2023Article
- Pharmacological effects and mechanisms of YiYiFuZi powder in chronic heart disease revealed by metabolomics and network pharmacology.Frontiers in molecular biosciences · 2023Article
- Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice.Cardiovascular research · 2021Article
- Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.Heart and vessels · 2021Observational
- Factors associated with elevated plasma phenylalanine in patients with heart failure.Amino acids · 2021Article
- Human Nitric Oxide Synthase-Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Elevated plasma phenylalanine predicts mortality in critical patients with heart failure.ESC heart failure · 2020Article
- Postoperative Atrial Fibrillation Following Cardiac Surgery: From Pathogenesis to Potential Therapies.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Review
- Amino Acid-Based Metabolic Profile Provides Functional Assessment and Prognostic Value for Heart Failure Outpatients.Disease markers · 2019Article
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- Amino Acid-Based Metabolic Panel Provides Robust Prognostic Value Additive to B-Natriuretic Peptide and Traditional Risk Factors in Heart Failure.Disease markers · 2018Article
- Association evidence of CCTTT repeat polymorphism in the iNOS promoter and the risk of atrial fibrillation in Taiwanese.Scientific reports · 2017Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsHeart failure is a common antecedent to atrial fibrillation; both heart failure and atrial fibrillation are associated with increased myocardial oxidative stress. Chronic canine heart failure reduces atrial action potential duration and atrial refractoriness. We hypothesized that inducible nitric oxide synthase 2 (NOS2) contributes to atrial oxidative stress and electrophysiologic alterations. METHODS AND
resultsA 16-week canine tachypacing model of heart failure was used (n= 21). At 10 weeks, dogs were randomized to either placebo (n = 12) or active treatment (n = 9) with NOS cofactor, tetrahydrobiopterin (BH(4), 50 mg), and NOS substrate (L-arginine, 3 g) twice daily for 6 weeks. A group of matched controls (n = 7) was used for comparison. Heart failure increased atrial NOS2 and reduced atrial BH(4), while L-arginine was unchanged. Treatment reduced inducible atrial fibrillation and normalized the heart failure-induced shortening of the left atrial myocyte action potential duration. Treatment increased atrial [BH(4)] while [L-arginine] was unchanged. Treatment did not improve left ventricular function or dimensions. Heart failure-induced reductions in atrial [BH(4)] resulted in NOS uncoupling, as measured by NO and superoxide anion (O(2)(·-)) production, while BH(4) and L-arginine treatment normalized NO and O(2)(·-). Heart failure resulted in left atrial oxidative stress, which was attenuated by BH(4) and L-arginine treatment.
conclusionChronic non-ischaemic heart failure results in atrial oxidative stress and electrophysiologic abnormalities by depletion of BH(4) and uncoupling of NOS2. Modulation of NOS2 activity by repletion of BH(4) may be a safe and effective approach to reduce the frequency of atrial arrhythmias during heart failure.
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