Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome

Purpose: Our objective was to evaluate L-arginine and nitric oxide metabolite (NOx) levels in children with sickle cell disease (SCD) at steady-state and during vaso-occlusive crisis (VOC). Because alterations in nitric oxide production may have an important role in the pathophysiology of SCD, our second aim was to determine if a relationship exists between these levels and vaso-occlusive crisis (VOC). Patients and Methods: Plasma L-arginine and serum NOx levels were examined in 36 patients with SCD with 39 episodes of VOC and 10 children with SCD at steady-state. Daily levels were obtained in children requiring hospitalization. Results: Steady-state L-arginine levels were normal in children with SCD. L-arginine levels were low, however, in children with VOC (37.4 +/- 2.7 vs. 53.6 +/- 4.6 mu mol/L; P = 0.008) but returned to baseline during hospitalization. In contrast, NOx levels were normal at presentation but decreased during hospitalization for both patients with VOC and patients with acute chest syndrome (ACS)(21.1 +/- 2.0, 17.4 +/- 2.4, and 12.3 +/- 1.6 mu mol/L, respectively; P < 0.05). In the patients with VOC who had ACS develop, L-arginine decreased to the lowest levels at the time of the ACS diagnosis, correlating with decreasing NOx levels. Conclusion: These data suggest that there may be a relationship between the L-arginine-nitric oxide pathway and vasoocclusion in SCD. Low arginine levels during VOC could reflect a state of acute substrate depletion that results in a decrease in nitric oxide production.