ReviewCritical care (London, England)2022
A new perspective on NO pathway in sepsis and ADMA lowering as a potential therapeutic approach.
Review in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 61 citations in OpenAlex.
- Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.Critical care (London, England) · 2023Trial
- Association of plasma ADMA, FABP4 levels, and AIP with increased cardiovascular disease risk in Graves' disease: an exploratory pilot study.BMC cardiovascular disorders · 2026Article
- CD74 deficiency protects against doxorubicin cardiotoxicity through RRM2-mediated regulation of ferroptosis.Acta pharmaceutica Sinica. B · 2026Article
- Preliminary investigation of circulating methaemoglobin fraction in cats with sepsis: a small exploratory study.Journal of feline medicine and surgery · 2026Article
- Supplementary parenteral arginine corrects hypoargininaemia and rebalances plasma amino acid profiles in very preterm infants receiving parenteral nutrition: A prospective study.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2026Article
- Rethinking Fluid Resuscitation in Septic Shock: A Phase-Adapted, Endothelium-Sparing Approach to Mitigate Capillary Leak.Journal of inflammation research · 2026Article
- Sepsis-Induced Cardiomyopathy and Cardiac Arrhythmias: Pathophysiology and Implications for Novel Therapeutic Approaches.Biomedicines · 2025Review
- Hypoxia-Inducible Factor 1-alpha (HIF1α), Nicotinamide Adenine Dinucleotide (NAD+, NADH), and Nitric Oxide (NO) interplay in critically ill patients, with implications for patient safety and targeted therapies: a review.Patient safety in surgery · 2025Review
- Association ofInternational journal of molecular sciences · 2025Article
- Immunomodulatory Effects of LSI312A on Dendritic Cells: A Novel Approach to Modulating Inflammatory Pathways.Journal of microbiology and biotechnology · 2025Article
- Quantitative Proteomics Reveals Fh15 as an Antagonist of TLR4 Downregulating the Activation of NF-κB, Inducible Nitric Oxide, Phagosome Signaling Pathways, and Oxidative Stress of LPS-Stimulated Macrophages.International journal of molecular sciences · 2025Article
- The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?Molecules (Basel, Switzerland) · 2025Review
- Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences.International journal of molecular sciences · 2025Review
- Pathogenesis and treatment strategies of sepsis-induced myocardial injury: modern and traditional medical perspectives.International journal of biological sciences · 2025Review
- Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study.Annals of intensive care · 2024Article
- In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.Journal of the American Heart Association · 2024Article
- Role of NO in Disease: Good, Bad or Ugly.Biomedicines · 2024Article
- Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis.Journal of biomedical science · 2024Review
- Limonene Exerts Anti-Inflammatory Effect on LPS-Induced Jejunal Injury in Mice by Inhibiting NF-κB/AP-1 Pathway.Biomolecules · 2024Article
- Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The nitric oxide pathway plays a critical role in vascular homeostasis. Increased levels of systemic nitric oxide (NO) are observed in preclinical models of sepsis and endotoxemia. This has led to the postulation that vasodilation by inducible nitric oxide synthase (iNOS) generated NO may be a mechanism of hypotension in sepsis. However, contrary to the expected pharmacological action of a nitric oxide synthase (NOS) inhibitor, clinical studies with L-NAME produced adverse cardiac and pulmonary events, and higher mortality in sepsis patients. Thus, the potential adverse effects of NO in human sepsis and shock have not been fully established. In recent years, the emerging new understanding of the NO pathway has shown that an endogenously produced inhibitor of NOS, asymmetric dimethylarginine (ADMA), a host response to infection, may play an important role in the pathophysiology of sepsis as well as organ damage during ischemia-reperfusion. ADMA induces microvascular dysfunction, proinflammatory and prothrombotic state in endothelium, release of inflammatory cytokines, oxidative stress and mitochondrial dysfunction. High levels of ADMA exist in sepsis patients, which may produce adverse effects like those observed with L-NAME. Several studies have demonstrated the association of plasma ADMA levels with mortality in sepsis patients. Preclinical studies in sepsis and ischemia-reperfusion animal models have shown that lowering of ADMA reduced organ damage and improved survival. The clinical finding with L-NAME and the preclinical research on ADMA "bed to bench" suggest that ADMA lowering could be a potential therapeutic approach to attenuate progressive organ damage and mortality in sepsis. Testing of this approach is now feasible by using the pharmacological molecules that specifically lower ADMA.
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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.