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 a nemia has mainly been attributed to increased levels of fetal hemoglobin (H bF), which reduces the tendency for sickle hemoglobin to polymerize, thereb y reducing the frequency of the vaso-occlusive phenomena associated with th e disease. However, benefits from HU treatment in patients have been report ed in advance of increased HbF levels. Thus, it has been suggested that oth er hydroxyurea-dependent mechanisms 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 human s. However, to our knowledge, evidence of nitric oxide production from HU m etabolism in humans has yet to be demonstrated. Here we report that oral ad ministration of HU for the treatment of sickle cell anemia produced detecta ble nitrosyl hemoglobin. The nitrosyl hemoglobin complex could be detected as early as 30 min after administration and persisted up to 4 h. Our observ ations support the hypothesis that the ability of HU to ease the vaso-occlu sive phenomena may, in part, be attributed to vasodilation and/or decreased platelet activation induced by HU-derived nitric oxide well in advance of increased HbF levels.