Protection of erythrocytes from sub-hemolytic mechanical damage by nitric oxide mediated inhibition of potassium leakage.
The effects of mechanical stress on red blood cell (RBC) deformability were evaluated by subjecting cells to a uniform fluid shear stress of 120 Pa for 15-120 seconds at 37 degrees C. This level of stress induced significant impairment of RBC deformability as assessed by ektacytometry, with the degree of impairment independent of extracellular calcium concentration. Inhibition of RBC nitric oxide (NO) synthesis by a competitive inhibitor of NO synthases (N-omega-nitro-L-arginine methyl ester, L-NAME) had no effect on deformability after exposure to mechanical stress. The NO donor sodium nitroprusside (SNP) prevented the deterioration of RBC deformability in a dose-dependent manner with 10(-4) M being the most effective concentration. A similar protective effect by the non-selective potassium channel blocker, tetraethylammonium chloride (TEA) suggests that the effect of NO might be mediated by the inhibition of potassium leakage from RBC. These results suggest that NO may prevent mechanical deterioration of RBC exposed to high shear stresses. While RBC are not exposed to such high levels of shear stresses for prolonged periods under normal circulatory conditions, comparable levels of mechanical stress can be encountered under certain situations (i.e., artificial organs, extracorporeal circulation) and may result in subhemolytic damage and hemorheological alterations.
Baskurt
Oguz K
OK
Department of Physiology, Akdeniz University Faculty of Medicine, Antalya, Turkey. baskurt@akdeniz.edu.tr
Uyuklu
Murat
M
Meiselman
Herbert J
HJ
D000328:Adult; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000097:blood*; D013314:Stress, Mechanical
D003470:Culture Media; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester