Nitric oxide effects

Arginine, the substrate for nitric oxide (NO) synthase (NOs) in the generation of NO, is low in the plasma of sickle cell anemia patients and also in sickle transgenic mice, suggesting increased need in the production of NO. In transgenic mice, NOs inhibitors result in increases in endothelial NOs and NO activity, leading to lower blood pressure and diminished arteriolar response to NO-mediated vasodilators. Low peripheral resistance has also been observed in sickle cell anemia patients.

Interestingly, recent data suggest that hydroxyurea, used in the treatment of these patients, is involved in the induction of Hb F, one of the ameliorating mechanisms associated with this drug.

Also, NO might be involved in the gender differences in severity observed in this disease. Females live longer and have higher levels of Hb F. Recent data demonstrate that NO availability and NO responsiveness are greater in women than in men with sickle cell disease and regulate the expression of adhesion molecules. Endothelium-dependent blood flows are largely non-NO-mediated in males.

We will return to the subject of NO in the next section (Treatment).

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