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Effects of nitric oxide and its congeners on sickle red blood cell deformability.
Transfusion. 2015 Oct; 55(10):2464-72.T

Abstract

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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Authors+Show Affiliations

Belanger AM
Department of Physics.
Keggi C
Department of Physics.
Kanias T
Heart, Lung, Blood and Vascular Medicine Institute. Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Gladwin MT
Heart, Lung, Blood and Vascular Medicine Institute. Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Kim-Shapiro DB
Department of Physics. Translational Science Center, Wake Forest University, Winston-Salem, North Carolina.

MeSH

Anemia, Sickle CellCalciumCalcium SignalingErythrocyte DeformabilityErythrocytes, AbnormalFemaleHumansMaleNitric OxideNitroprussidePotassium

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25912054

Citation

Belanger, Andrea M., et al. "Effects of Nitric Oxide and Its Congeners On Sickle Red Blood Cell Deformability." Transfusion, vol. 55, no. 10, 2015, pp. 2464-72.
Belanger AM, Keggi C, Kanias T, et al. Effects of nitric oxide and its congeners on sickle red blood cell deformability. Transfusion. 2015;55(10):2464-72.
Belanger, A. M., Keggi, C., Kanias, T., Gladwin, M. T., & Kim-Shapiro, D. B. (2015). Effects of nitric oxide and its congeners on sickle red blood cell deformability. Transfusion, 55(10), 2464-72. https://doi.org/10.1111/trf.13134
Belanger AM, et al. Effects of Nitric Oxide and Its Congeners On Sickle Red Blood Cell Deformability. Transfusion. 2015;55(10):2464-72. PubMed PMID: 25912054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of nitric oxide and its congeners on sickle red blood cell deformability. AU - Belanger,Andrea M, AU - Keggi,Christian, AU - Kanias,Tamir, AU - Gladwin,Mark T, AU - Kim-Shapiro,Daniel B, Y1 - 2015/04/23/ PY - 2015/01/15/received PY - 2015/03/11/revised PY - 2015/03/23/accepted PY - 2015/4/28/entrez PY - 2015/4/29/pubmed PY - 2016/1/26/medline SP - 2464 EP - 72 JF - Transfusion JO - Transfusion VL - 55 IS - 10 N2 - 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. SN - 1537-2995 UR - https://www.unboundmedicine.com/medline/citation/25912054/Effects_of_nitric_oxide_and_its_congeners_on_sickle_red_blood_cell_deformability_ DB - PRIME DP - Unbound Medicine ER -