Effect of Membrane Permeability and Extracellular Diffusion on NO uptake by Erythrocytes

Abstract

Quantification of nitric oxide (NO)‐red blood cells (RBC) reaction metabolites is necessary to evaluate the extent of diffusional resistances for nitric oxide transport in vascular lumen. Delivery of physiologically relevant concentration of nitric oxide and RBC‐hemoglobin are a critical factor in quantification of in vitro NO‐RBC reaction. In this study, we developed a flask bioreactor which delivers gaseous NO to the RBCs and studied the effects of hematocrit (hct) and NO concentrations on NO‐RBC interactions. We developed a computational model of NO transport to single RBCs using experimental data to analyze the effect of RBC membrane permeability on steady state NO concentrations in the bulk of liquid surrounding the RBCs and at the RBC membrane. We observed that the steady state NO concentrations in the bulk of liquid and at the RBC membrane 1) decreased with increase in RBC membrane permeability for a given equilibrium NO concentration and hct; 2) increased with increase available NO concentrations at a given RBC membrane permeability; 3) decreased with increase in hct for a given RBC membrane permeability. Our results indicate that the extracellular diffusion and RBC membrane permeability are significant diffusional barriers for NO transport to the RBCs and the RBC NO membrane permeability should be in the range of 0.0415‐ 0.4 cm/s. Supported by: AHA 0530050N, NIH R01 HL084337 & R15 HL087287.