ArticleBlood2006
Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01231165 (Comparative Randomized Single-blind Trial of Amiloride in Coronary Heart Disease), which is not on this map. Cited by 181 papers, 1 of them a synthesis that pooled it.
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.
Comparative Randomized Single-blind Trial of Amiloride in Coronary Heart Disease
Who cites it
181 citing papers in PubMed, 1 synthesis or guideline pooled it, 494 citations in OpenAlex.
- Efficacy of red yeast rice extract on myocardial infarction patients with borderline hypercholesterolemia: A meta-analysis of randomized controlled trials.Scientific reports · 2020Pooled it
- The acute effects of exercise intensity and inorganic nitrate supplementation on vascular health in females after menopause.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Trial
- Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP.The Journal of clinical investigation · 2023Trial
- Sickle cell microvascular paradox-oxygen supply-demand mismatch.American journal of hematology · 2019Trial
- Acute ingestion of dietary nitrate increases muscle blood flow via local vasodilation during handgrip exercise in young adults.Physiological reports · 2018Trial
- Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.Journal of the American Heart Association · 2017Trial
- Dietary nitrate accelerates postexercise muscle metabolic recovery and O2 delivery in hypoxia.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Trial
- Impact of mental and physical stress on blood pressure and pulse pressure under normobaric versus hypoxic conditions.PloS one · 2014Trial
- Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite.British journal of pharmacology · 2013Trial
- Sodium nitrite promotes regional blood flow in patients with sickle cell disease: a phase I/II study.British journal of haematology · 2008Trial
- The pyruvate kinase activator etavopivat (FT-4202) limits pulmonary and systemic sequelae of sepsis in a mouse LPS model.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- L-Arginine and Nitric Oxide in Vascular Regulation-Experimental Findings in the Context of Blood Donation.Nutrients · 2025Review
- White blood cell-to-haemoglobin ratio as a predictor of 30-day mortality in ICU patients with pulmonary hypertension: a MIMIC-IV database study.BMC cardiovascular disorders · 2024Observational
- The chemical biology of dinitrogen trioxide.Redox biochemistry and chemistry · 2024Article
- Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species.International journal of molecular sciences · 2024Review
- Inhaled NO at a crossroads in cardiac surgery: current need to improve mechanistic understanding, clinical trial design and scientific evidence.Frontiers in cardiovascular medicine · 2024Review
- Interstitial Lung Disease in Patients with Mixed Connective Tissue Disease: A Retrospective Study.International journal of general medicine · 2024Article
- Mechanisms and physiological function of daily haemoglobin oxidation rhythms in red blood cells.The EMBO journal · 2023Article
- Photostimulation of brain lymphatics in male newborn and adult rodents for therapy of intraventricular hemorrhage.Nature communications · 2023Article
121 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
13 authors at 1 institution in 1 country.
Funding
Abstract
Local vasodilation in response to hypoxia is a fundamental physiologic response ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell (RBC), with hemoglobin the hypoxic sensor. Herein, we investigate the mechanisms regulating this process and explore the relative roles of adenosine triphosphate, S-nitrosohemoglobin, and nitrite as effectors. We provide evidence that hypoxic RBCs mediate vasodilation by reducing nitrite to nitric oxide (NO) and ATP release. NO dependence for nitrite-mediated vasodilation was evidenced by NO gas formation, stimulation of cGMP production, and inhibition of mitochondrial respiration in a process sensitive to the NO scavenger C-PTIO. The nitrite reductase activity of hemoglobin is modulated by heme deoxygenation and heme redox potential, with maximal activity observed at 50% hemoglobin oxygenation (P(50)). Concomitantly, vasodilation is initiated at the P(50), suggesting that oxygen sensing by hemoglobin is mechanistically linked to nitrite reduction and stimulation of vasodilation. Mutation of the conserved beta93cys residue decreases the heme redox potential (ie, decreases E(1/2)), an effect that increases nitrite reductase activity and vasodilation at any given hemoglobin saturation. These data support a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose "enzyme activity" couples hypoxia to increased NO-dependent blood flow.
Indexed as
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What OpenQuestion holds
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.