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Nitroprusside inhibits calcium‐induced impairment of red blood cell deformability
Author(s) -
Barodka Viachaslau,
Mohanty Joy G.,
Mustafa Asif K.,
Santhanam Lakshmi,
Nyhan Aoibhinn,
Bhunia Anil K.,
Sikka Gautam,
Nyhan Daniel,
Berkowitz Dan E.,
Rifkind Joseph M.
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12291
Subject(s) - sodium nitroprusside , chemistry , nitric oxide , red blood cell , erythrocyte deformability , extracellular , calcium , potassium channel , biophysics , intracellular , pharmacology , endocrinology , medicine , biochemistry , biology , organic chemistry
Background Red blood cell ( RBC ) deformation is critical for microvascular perfusion and oxygen delivery to tissues. Abnormalities in RBC deformability have been observed in aging, sickle cell disease, diabetes, and preeclampsia. Although nitric oxide ( NO ) prevents decreases in RBC deformability, the underlying mechanism is unknown. Study Design and Methods As an experimental model, we used ionophore A 23187–mediated calcium influx in RBC s to reduce their deformability and investigated the role of NO donor sodium nitroprusside ( SNP ) and KCa 3.1 ( G ardos) channel blockers on RBC deformability (measured as elongation index [ EI ] by microfluidic ektacytometry). RBC intracellular Ca 2+ and extracellular K + were measured by inductively coupled plasma mass spectrometry and potassium ion selective electrode, respectively. Results SNP treatment of RBCs blocked the Ca 2+ (approx. 10 μ mol/L )‐induced decrease in RBC deformability ( EI 0.34 ± 0.02 vs . 0.09 ± 0.01, control vs . Ca 2+ loaded, p < 0.001; and EI 0.37 ± 0.02 vs . 0.30 ± 0.01, SNP vs . SNP plus Ca 2+ loaded) as well as Ca 2+ influx and K + efflux. The SNP effect was similar to that observed after pharmacologic blockade of the KCa 3.1 channel (with charybdotoxin or extracellular medium containing isotonic K + concentration). In RBCs from KCa 3.1 –/– mice, 10 μmol/ L Ca 2+ loading did not decrease cellular deformability. A preliminary attempt to address the molecular mechanism of SNP protection suggests the involvement of cell surface thiols. Conclusion Our results suggest that nitroprusside treatment of RBC s may protect them from intracellular calcium increase–mediated stiffness, which may occur during microvascular perfusion in diseased states, as well as during RBC storage.