Nitric oxide availability is reduced in sickle cell disease even in presence of low amounts of intravascular cell‐free hemoglobin

Abstract

Cell‐free Hb is released by intravascular hemolysis in sickle cell disease and can affect the nitric oxide availability. Role of small amounts of cell‐free Hb in lowering NO availability and thereby the development of pulmonary hypertension seen in sickle cell disease has been questioned. To analyze the effect of intravascular cell‐free Hb on NO availability under sickle cell disease conditions, we developed a mathematical model describing NO transport in a 50 μm arteriole. Simulations were performed to assess the significance of cell free layer thickness, blood velocity and NO‐RBC reaction rate constant on NO bioavailability. We observed that NO bioavailability was lower under sickle cell conditions as compared to physiological conditions. In presence of 0.5 μM cell‐free Hb, NO bioavailability reduced ~3 to 7 fold. Increasing cell free layer thickness did not increase NO availability significantly for cell‐free Hb concentrations ≥ 1 μM. Our results indicate that intravascular cell‐free Hb concentrations as low as 0.5 μM can reduce the NO availability significantly and in presence of cell‐free Hb ≥ 1 μM, diffusional resistance for NO transport from the cell free layer become less significant. Thus, a low amount of cell‐free Hb reduces NO availability and may contribute to the development of sickle cell complications of pulmonary hypertension. Supported by AHA 0530050N & R15 HL087287 grants.