ArticleCirculation research2007
Nitroxyl improves cellular heart function by directly enhancing cardiac sarcoplasmic reticulum Ca2+ cycling.
Article in Circulation research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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.
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Who cites it
93 citing papers in PubMed, 215 citations in OpenAlex.
- A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.Journal of clinical pharmacology · 2019Trial
- A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.European journal of heart failure · 2017Trial
- Nitroxyl (HNO): A novel approach for the acute treatment of heart failure.Circulation. Heart failure · 2013Trial
- Real-time photoactivated SRS imaging enables spatiotemporally controlled nitroxyl release and therapeutic guidance in vivo.Nature communications · 2026Article
- Fluorofenidone ameliorates pressure overload-induced heart failure by stabilizing SERCA2a in male mice.Nature communications · 2026Article
- Oxidative HNO Formation Mechanisms from NHACS omega · 2025Article
- Electronic Modification of a Reduced Mononuclear Nonheme Iron Nitrosyl Complex Leads to HNO Release.Journal of the American Chemical Society · 2025Article
- Article
- Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases.Biomolecules · 2025Review
- Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump.Frontiers in cardiovascular medicine · 2023Review
- Cardioprotective actions of nitroxyl donor Angeli's salt are preserved in the diabetic heart and vasculature in the face of nitric oxide resistance.British journal of pharmacology · 2022Article
- Reactive Oxygen Species Induced Pathways in Heart Failure Pathogenesis and Potential Therapeutic Strategies.Biomedicines · 2022Review
- Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds.Molecules (Basel, Switzerland) · 2021Review
- Nitroaromatic Antibiotics as Nitrogen Oxide Sources.Biomolecules · 2021Review
- Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation.Handbook of experimental pharmacology · 2021Review
- Article
- Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents.The Journal of biological chemistry · 2020Article
- Mechanisms Associated to Nitroxyl (HNO)-Induced Relaxation in the Intestinal Smooth Muscle.Frontiers in physiology · 2020Article
- Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling.Frontiers in pharmacology · 2020Review
- Treatments targeting inotropy.European heart journal · 2019Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca(2+). A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca(2+) pump and the ryanodine receptor 2, leading to increased Ca(2+) uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca(2+)-release channels and accelerates Ca(2+) reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca(2+) transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca(2+) cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of 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.