Effect of nitric oxide on deformability of sickle erythrocytes.

摘要

Nitric oxide (NO) is being proposed as the basis of treatments for several diseases including sickle cell disease. Despite its important physiological functions, No's bioactivity is not well understood. A radical rethink of NO bioactivity was called for based mainly on the work of Andrew Gow, Jonathon Stamler and coworkers. We added NO to hemoglobin in both 0.1 M and 0.01 M phosphate buffer as well as to whole blood. We found that the reaction rates of HbNO formation and metHb formation are independent of oxygen saturation. Our results dismiss the idea of cooperative binding of NO to hemoglobin and we find that there is no need of such a radical rethink. Using a flash-flow photolysis technique we have determined that the rate of NO binding to normal adult R-state hemoglobin is essentially the same as that reported for T-state NO binding. These data further support the noncooperative binding of NO to R-state oxyHb.; To quantify any possible physiological NO effects on the erythrocyte deformability, we measured the kinetics of changes in the deformability of deoxygenated sickle erythrocytes when they are exposed to O₂ or CO using a flow-channel laser diffraction technique. We found that the deformability of deoxygenated sickle erythrocytes did not regain their optimal value for several seconds after mixing. These data indicate incomplete HbS polymer melting during the second or so at the lungs, and the polymers may persist during arterial circulation in vivo.; Using the flow-channel laser diffraction techniques, we measured the deformability change of normal erythrocytes as a function of NO added after the erythrocytes had been incubated with NO for up to an hour. We found the change is minimal and there is no consistent trends. Thus, we conclude that there is no direct effect of NO on the deformability of the normal erythrocytes. Xu et al showed that NO has no direct solubilizing effect on HbS. Taken together, we suggest that there may not be any direct effect of physiological levels of NO on the deformability of sickle erythrocytes.