Biological action of nitric oxide donor compounds on platelets from patients with sickle cell disease.
Several lines of evidence point to the potential role of nitric oxide (NO) in the pathophysiology, as well as in the therapy, of sickle cell disease (SCD). In this study, we compared the effects of NO on platelets from normal individuals and from patients with SCD. Three NO donors were used to deliver NO to platelets: sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine (CysNO) and sodium trioxdintrate (OXINO or Angeli's salt). ADP-induced platelet aggregation, CD62P expression, PAC-1 binding and calcium elevation were evaluated in paired studies of normal and SCD subjects. DEANO significantly reduced aggregation in SCD platelets compared with normal platelets. DEANO similarly reduced the extent of CD62P expression in SCD platelets. All NO donors reduced PAC-1 binding, but there were no significant differences between platelets from normal or SCD subjects. Calcium elevation, as induced by ADP, was not altered by the presence of NO donors. However, when platelets were stimulated with thrombin, there was an increased initial response of SCD platelets compared with normal platelets. Taken together, these data suggest that the mode of NO delivery to platelets may produce various physiological responses and the optimization of NO delivery may contribute to reducing platelet aggregation in sickle cell disease.
Mondoro
T H
TH
Laboratory of Cellular Hematology and Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drugs Administration, National Institutes of Health, Bethesda, MD 20892, USA.
Ryan
B B
BB
Hrinczenko
B W
BW
Schechter
A N
AN
Vostal
J G
JG
Alayash
A I
AI
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D054641:Dual Specificity Phosphatase 2; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009573:Nitrites / Q000494:pharmacology; D009589:Nitrogen Oxides; D009603:Nitroso Compounds / Q000494:pharmacology; D019007:P-Selectin / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects*; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D026403:S-Nitrosothiols; D012805:Sickle Cell Trait / Q000097:blood*; D013917:Thrombin / Q000494:pharmacology
D004048:Diethylamines; D006490:Hemostatics; D020030:Nitric Oxide Donors; D009573:Nitrites; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D019007:P-Selectin; D026403:S-Nitrosothiols; C021229:oxyhyponitrite; D000244:Adenosine Diphosphate; C021315:S-nitrosocysteine; C087229:diethylamine dinitric oxide adduct; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D013917:Thrombin; D003545:Cysteine; D002118:Calcium