Effects of nitric oxide and its congeners on sickle red blood cell deformability
Open accessAbstract
BACKGROUND: Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium‐activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs). STUDY DESIGN AND METHODS: RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser‐assisted osmotic gradient ektacytometry. RESULTS: Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium‐induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation‐induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. CONCLUSION: These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease.
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The effects of NO donors on RBC deformability ex vivo were not confirmed by others.
“However, recently, the effects of NO donors on RBCs deformability ex vivo were not confirmed by others (15).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [15]
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Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia
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- Authors
- Belanger, A. M., Keggi, C., Kanias, T., Gladwin, M. T., & Kim‐Shapiro, D. B.
- Affiliations
- Department of Physics
- University of Pittsburgh (US)
- Wake Forest University (US)
- Corresponding author
- Kim‐Shapiro, Daniel B.
- Venue
- Transfusion
- Publisher
- Wiley
- Published
- 2015-04-23
- Volume
- 55
- Issue
- 10
- Pages
- 2464-2472
- ISSN
- 0041-1132 (ISSN-L)
- 1537-2995
- PMC
- PMC4605849
- OpenAlex
- W2161988331
- Cited by
- 37
- References
- 26
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 1
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Transfusion (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (HL058091, HL098032, T32 GM095440)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Keywords
- sickle cell disease, sickle red blood cells, erythrocyte deformability, nitric oxide, sodium nitroprusside, sodium nitrite, Gardos channel, potassium efflux, calcium influx, red blood cell dehydration, hemoglobin polymerization, oxygen partial pressure
- MeSH terms
- Anemia, Sickle Cell, Calcium, Erythrocyte Deformability, Erythrocytes, Abnormal, Female, Humans, Male, Nitric Oxide, Nitroprusside, Potassium, Calcium Signaling
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