US EPA

2831187 

Journal Article 

Effects of nitric oxide and its congeners on sickle red blood cell deformability 

Belanger, AM; Keggi, C; Kanias, T; Gladwin, MT; Kim-Shapiro, DB 

2015 

1 

Transfusion
ISSN: 0041-1132
EISSN: 1537-2995 

55 

10 

2464-2472 

English 

25912054 

10.1111/trf.13134 

WOS:000362914500022 

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.