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


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.


CONCLUSIONS
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.
Department of Physics.
Andrea M
AM
Belanger
Department of Physics.
Christian
C
Keggi
Heart, Lung, Blood and Vascular Medicine Institute.|Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Tamir
T
Kanias
Heart, Lung, Blood and Vascular Medicine Institute.|Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Mark T
MT
Gladwin
Department of Physics.|Translational Science Center, Wake Forest University, Winston-Salem, North Carolina.
Daniel B
DB
Kim-Shapiro
D000755:Anemia, Sickle Cell / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004913:Erythrocytes, Abnormal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism
D009599:Nitroprusside; D009569:Nitric Oxide; D011188:Potassium; D002118:Calcium