Role of erythrocytes in vascular nitric oxide homeostasis

Nitric oxide (NO) bioavailability is maintained in vasculature despite the presence of large quantities of NO scavenging hemoglobin present in RBCs due to the reduced NO consumption by RBCs, owing to the transport resistances for NO to reach RBC bound Hb. However, the extent of reduction in NO consumption by RBCs and individual contributions of transfer resistances are still not clear. The present study analyses the NO‐RBC interactions to determine effective NO‐RBC reaction rate constant and the effect of RBC membrane permeability and extracellular diffusional resistances on NO uptake by RBCs by integrating experimental and computational methods. RBC membrane permeability estimate was in the range of 0.0415‐0.4 cm/s and NO‐RBC interaction products increased with NO concentrations indicating that RBC membrane permeability and extracellular diffusion provide significant resistance for NO transport to RBCs. We predicted ~7 times lower effective NO‐RBC reaction rate constant (0.2×10 5 M −1 s −1 ) than the previously reported NO‐RBC reaction rate constant. In our next study, we simulated NO transport in arteriole to study the effect of the lower NO‐RBC reaction rate constant on NO bioavailability in microcirculation. Our results showed an increased luminal and abluminal NO bioavailability for NO‐RBC reaction rate constant of 0.2×10 5 M −1 s −1 and downstream transport of NO was possible in the arteriole.