title: Contribution of membrane permeability and unstirred layer diffusion to nitric oxide-red blood cell interaction.
abstract: Nitric oxide (NO) consumption by red blood cell (RBC) hemoglobin (Hb) in vasculature is critical in regulating the vascular tone. The paradox of NO production at endothelium in close proximity of an effective NO scavenger Hb in RBCs is mitigated by lower NO consumption by RBCs compared to that of free Hb due to transport resistances including membrane resistance, extra- and intra-cellular resistances for NO biotransport to the RBC. Relative contribution of each transport resistance on NO-RBC interactions is still not clear. We developed a mathematical model of NO transport to a single RBC to quantify the contributions from individual transport barriers by analyzing the effect of RBC membrane permeability (P(m)), hematocrit (Hct) and NO-Hb reaction rate constants on NO-RBC interactions. Our results indicated that intracellular diffusion of NO was not a rate limiting step for NO-RBC interactions. The extracellular diffusion contributed 70-90% of total transport resistance for P(m)>1 cm s(-1) whereas membrane resistance accounts for 50-75% of total transport resistance for P(m)<0.1 cm s(-1). We propose a narrow P(m) range of 0.21-0.44 cm s(-1) for 10-45% Hct, respectively, below which membrane resistance is more significant and above which extracellular diffusion is a dominating transport resistance for NO-RBC interactions.
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, 5050 Anthony Wayne Dr., #2152 Engineering, MI 48202, USA. ep3439@wayne.edu
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Deonikar
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kavdia
mesh_terms: D001692:Biological Transport; D002450:Cell Communication; D002463:Cell Membrane Permeability / Q000502:physiology*; D004058:Diffusion; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide