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The pain of sickle cell

Cell free hemoglobin diverts NO from smooth-muscle vascular cells in sickle-cell disease.

Tudor Toma

Nitric oxide gas has a short half-life and is produced by vascular endothelial cells where it is responsible for controlling vascular muscle tone. The interaction between NO and cell free hemoglobin released during chronic hemolytic diseases such as sickle-cell disease have been poorly understood. In November 11 Nature Medicine, Christopher Reiter and colleagues at the National Institutes of Health, Bethesda, USA, show that in sickle-cell disease cell-free ferrous hemoglobin consumes the NO produced by endothelial cells, diverting it from smooth-muscle cells (Nature Medicine, DOI:10.1038/nm799, November 11, 2002).

Reiter et al. observed that plasma from patients with sickle-cell disease contains cell-free ferrous hemoglobin, which stoichiometrically consumes micromolar quantities of NO and abrogates forearm blood flow responses to NO donor infusions. In addition, they showed that drugs that inactivate plasma hemoglobin by oxidation or NO ligation restore the bioavailability of NO.

"These results may help explain the vascular complications...

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