Detection of nitrosyl hemoglobin in venous blood in the treatment of sickle cell anemia with hydroxyurea

The clinical efficacy of hydroxyurea (HU) in the treatment of sickle cell anemia has mainly been attributed to increased levels of fetal hemoglobin (HbF), which reduces the tendency for sickle hemoglobin to polymerize, thereby reducing the fre-quency of the vaso-occlusive phenomena associated with the disease. However, benefits from HU treatment in patients have been reported in advance of increased HbF levels. Thus, it has been suggested that other hydroxyurea-dependent mecha-nisms may, in part, account for its clinical efficacy. We have previously demonstrated that HU is metabolized in rats to release nitric oxide and, therefore, postulated the same to occur in humans. However, to our knowledge, evidence of nitric oxide production from HU metabolism in humans has yet to be demonstrated. Here we report that oral administration of HU fo