Role of membrane permeability and extracellular diffusion in nitric oxide transport to the red blood cells

Abstract

Nitric oxide (NO) availability for vasodilation in vasculature is dependent on its consumption by red blood cell (RBC) hemoglobin. Extracellular diffusion in the plasma, cell free layer near the vessel wall and the RBC membrane permeability (Pm) reportedly lower NO consumption by RBCs. To understand the contribution of RBC membrane permeability and extracellular diffusion from the plasma layer surrounding the RBC towards NO uptake by RBCs, we developed a mathematical model simulating NO transport to a single RBC. Simulations were performed for Pm values ranging from 0.0415–40 cm/s and hematocrit (Hct) ranging from 1–45% and NO concentrations at the RBC membrane (CNOm inside and CNOm outside) were estimated. NO concentration gradients in the plasma layer increased with Pm. CNOm inside increased while CNOm outside decreased with Pm. At Pm =40 cm/s, CNOm inside and CNOm outside were similar to each other and both increased with Hct, indicating that extracellular diffusional resistance provides a significant transport barrier for NO at higher RBC membrane permeability. At Pm = 0.0415 cm/s, estimated CNOm outside were much higher than CNOm inside and both were independent of Hct for Hct ≥ 15%, suggesting that at lower RBC membrane permeability, for Hct ≥ 15%, RBC permeability is a major barrier for resistance for NO transport. Insights from this study may prove useful in understanding interaction of NO with RBC. Supported by AHA 0530050N & R15 HL087287 grants.