Th. Mondoro et al., Biological action of nitric oxide donor compounds on platelets from patients with sickle cell disease, BR J HAEM, 112(4), 2001, pp. 1048-1054
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 deliv
er NO to platelets: sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO
), S-nitrosocysteine (CysNO) and sodium trioxdintrate (OXINO or Angeli's sa
lt). ADP-induced platelet aggregation, CD62P expression, PAC-1 binding and
calcium elevation were evaluated in paired studies of normal and SCD subjec
ts. 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 sign
ificant 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 increa
sed 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 deliver
y may contribute to reducing platelet aggregation in sickle cell disease.