ReviewCirculation research2020
Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle.
Review in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 132 citations in OpenAlex.
- Effects of administration of sildenafil citrate and amino acids on selected physiological, blood gas and biochemical parameters in pregnant twin-bearing sheep in late gestation.Veterinary and animal science · 2026Article
- Red Blood Cells in Normal and Pathological States: Redox Reactions of Hemoglobin.Molecules (Basel, Switzerland) · 2026Review
- NO- and S-nitrosothiols-dependent relaxation in large and small resistance blood vessels.Frontiers in physiology · 2026Review
- Neurovascular Signaling at the Gliovascular Interface: From Flow Regulation to Cognitive Energy Coupling.International journal of molecular sciences · 2025Review
- The Challenge of Measuring Exercise: Advancing Metrological Barriers in Wearable Sensing.JMIR mHealth and uHealth · 2025Review
- Optimizing post brain death vascularized composite graft quality through ex vivo restoration of S-nitrosothiol homeostasis.Scientific reports · 2025Article
- Continuous Monitoring of Muscle Oxygenation in Endurance Athletes During Incremental Cycling: Experimental Validation of a Wearable Continuous-Wave NIRS Sensor Using Frequency-Domain Near-Infrared Spectroscopy.Bioengineering (Basel, Switzerland) · 2025Article
- Dysregulated ProteinCirculation research · 2025Article
- S-nitrosylation of pVHL regulates βProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Piezo1 activates nitric oxide synthase in red blood cells via protein kinase C with increased activity in diabetes.Mechanobiology in medicine · 2025Article
- S-Nitrosylation in Cardiovascular Disorders: The State of the Art.Biomolecules · 2025Review
- Reactive Nitrogen Species and Fibrinogen: Exploring the Effects of Nitration on Blood Clots.Antioxidants (Basel, Switzerland) · 2025Review
- Evolved changes in reflex control of the cardiovascular system in deer mice native to high altitude.The Journal of experimental biology · 2025Article
- Iron deficiency anemia in pregnancy and related complications with specific insight in Rivers State, Nigeria: a narrative review.Annals of medicine and surgery (2012) · 2025Review
- Artificial blood-hope and the challenges to combat tumor hypoxia for anti-cancer therapy.Medical & biological engineering & computing · 2025Review
- Nitric oxide: Potential therapeutic target in Heat Stress-induced Multiple Organ Dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.Nutrients · 2025Review
- Preoperative serum indicators as predictors of postoperative hypoparathyroidism following thyroidectomy.Frontiers in endocrinology · 2025Article
- Erythrocytes enhance oxygen-carrying capacity through self-regulation.Frontiers in physiology · 2025Review
- The Roles of Oxidative Stress and Red Blood Cells in the Pathology of the Varicose Vein.International journal of molecular sciences · 2024Review
3 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
4 authors at 1 institution in 1 country.
Funding
Abstract
A continuous supply of oxygen is essential for the survival of multicellular organisms. The understanding of how this supply is regulated in the microvasculature has evolved from viewing erythrocytes (red blood cells [RBCs]) as passive carriers of oxygen to recognizing the complex interplay between Hb (hemoglobin) and oxygen, carbon dioxide, and nitric oxide-the three-gas respiratory cycle-that insures adequate oxygen and nutrient delivery to meet local metabolic demand. In this context, it is blood flow and not blood oxygen content that is the main driver of tissue oxygenation by RBCs. Herein, we review the lines of experimentation that led to this understanding of RBC function; from the foundational understanding of allosteric regulation of oxygen binding in Hb in the stereochemical model of Perutz, to blood flow autoregulation (hypoxic vasodilation governing oxygen delivery) observed by Guyton, to current understanding that centers on S-nitrosylation of Hb (ie, S-nitrosohemoglobin; SNO-Hb) as a purveyor of oxygen-dependent vasodilatory activity. Notably, hypoxic vasodilation is recapitulated by native S-nitrosothiol (SNO)-replete RBCs and by SNO-Hb itself, whereby SNO is released from Hb and RBCs during deoxygenation, in proportion to the degree of Hb deoxygenation, to regulate vessels directly. In addition, we discuss how dysregulation of this system through genetic mutation in Hb or through disease is a common factor in oxygenation pathologies resulting from microcirculatory impairment, including sickle cell disease, ischemic heart disease, and heart failure. We then conclude by identifying potential therapeutic interventions to correct deficits in RBC-mediated vasodilation to improve oxygen delivery-steps toward effective microvasculature-targeted therapies. To the extent that diseases of the heart, lungs, and blood are associated with impaired tissue oxygenation, the development of new therapies based on the three-gas respiratory system have the potential to improve the well-being of millions of patients.
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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.