ArticlePloS one2014
The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- RRx-001: a chimeric triple action NLRP3 inhibitor, Nrf2 inducer, and nitric oxide superagonist.Frontiers in oncology · 2023Review
- Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19.Seminars in oncology · 2020Article
- Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.Nitric oxide : biology and chemistry · 2020Article
- Nitrite pharmacokinetics, safety and efficacy after experimental ventricular fibrillation cardiac arrest.Nitric oxide : biology and chemistry · 2019Article
- The role of nitrite in muscle function, susceptibility to contraction injury, and fatigability in sickle cell mice.Nitric oxide : biology and chemistry · 2018Article
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- The macrophage stimulating anti-cancer agent, RRx-001, protects against ischemia-reperfusion injury.Expert review of hematology · 2017Article
- Emerging targets for radioprotection and radiosensitization in radiotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Targeting tumor hypoxia with the epigenetic anticancer agent, RRx-001: a superagonist of nitric oxide generation.Medical oncology (Northwood, London, England) · 2016Article
- A look inside the mechanistic black box: Are red blood cells the critical effectors of RRx-001 cytotoxicity?Medical oncology (Northwood, London, England) · 2016Article
- NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001.Redox biology · 2015Review
- From METS to malaria: RRx-001, a multi-faceted anticancer agent with activity in cerebral malaria.Malaria journal · 2015Article
- Rewriting the epigenetic code for tumor resensitization: a review.Translational oncology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nitric oxide (NO) is a key regulator of vascular tone. Endothelial nitric oxide synthase (eNOS) is responsible for NO generation under normoxic conditions. Under hypoxia however, eNOS is inactive and red blood cells (RBC) provide an alternative NO generation pathway from nitrite to regulate hypoxic vasodilation. While nitrite reductase activity of hemoglobin is well acknowledged, little is known about generation of NO by intact RBC with physiological hemoglobin concentrations. We aimed to develop and apply a new approach to provide insights in the ability of RBC to convert nitrite into NO under hypoxic conditions. We established a novel experimental setup to evaluate nitrite uptake and the release of NO from RBC into the gas-phase under different conditions. NO measurements were similar to well-established clinical measurements of exhaled NO. Nitrite uptake was rapid, and after an initial lag phase NO release from RBC was constant in time under hypoxic conditions. The presence of oxygen greatly reduced NO release, whereas inhibition of eNOS and xanthine oxidoreductase (XOR) did not affect NO release. A decreased pH increased NO release under hypoxic conditions. Hypothermia lowered NO release, while hyperthermia increased NO release. Whereas fetal hemoglobin did not alter NO release compared to adult hemoglobin, sickle RBC showed an increased ability to release NO. Under all conditions nitrite uptake by RBC was similar. This study shows that nitrite uptake into RBC is rapid and release of NO into the gas-phase continues for prolonged periods of time under hypoxic conditions. Changes in the RBC environment such as pH, temperature or hemoglobin type, affect NO release.
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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.