A Model of NO/O2 Transport in Capillary-perfused Tissue Containing an Arteriole and Venule Pair

Chen, Xuewen; Buerk, Donald G.; Barbee, Kenneth A.; Jaron, Dov

doi:10.1007/s10439-006-9236-z

Cited by 48 publications

(60 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 1994, Lancaster (57) constructed a computational model to simulate the diffusion and reaction of NO in a system mimicking the endothelium and its surrounding tissue. Vaughn (20,21,29,42,47,48,105). Generally, these theoretic models predict an ϳ100-nM level of NO near an arteriole.…”

Section: Variation In Perivascular No Concentration C Nomentioning

confidence: 99%

Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective

Chen

Pittman

Popel³

2008

Antioxidants & Redox Signaling

238

175

View full text Add to dashboard Cite

Nitric oxide (NO) affects two key aspects of O 2 supply and demand: It regulates vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the vascular smooth muscle, and it controls mitochondrial O 2 consumption by inhibiting cytochrome c oxidase. However, significant gaps exist in our quantitative understanding of the regulation of NO production in the vascular region. Large apparent discrepancies exist among the published reports that have analyzed the various pathways in terms of the perivascular NO concentration, the efficacy of NO in causing vasodilation (EC 50 ), its efficacy in tissue respiration (IC 50 ), and the paracrine and endocrine NO release. In this study, we review the NO literature, analyzing NO levels on various scales, identifying and analyzing the discrepancies in the reported data, and proposing hypotheses that can potentially reconcile these discrepancies. Resolving these issues is highly relevant to improving our understanding of vascular biology and to developing pharmaceutical agents that target NO pathways, such as vasodilating drugs.

show abstract

Section: Variation In Perivascular No Concentration C Nomentioning

confidence: 99%

Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective

Chen

Pittman

Popel³

2008

Antioxidants & Redox Signaling

238

175

View full text Add to dashboard Cite

show abstract

“…with the reference NO production rate (R NO,ref ) = 150 lM/ s (used in our previous models [11,12]) relative to WSS (s w,ref ) = 24 dyn/cm 2 . This reference WSS was used by Kavdia and Popel [26] for shear-dependent rate of NO release from the endothelium in their single arteriole model.…”

Section: Wss-dependent No Productionmentioning

confidence: 99%

“…A number of NO transport models have been developed based on single arterioles or arteriole-venule pairs [7,11,12,26,27,32,33,50,51], with earlier models reviewed by Buerk [4] and more recent models reviewed by Tsoukias [47]. For example, a 2D diffusion model in cylindrical coordinates by Kavdia and Popel [26] included the effect of WSS on R NO to predict vascular wall NO for a 50 lm diameter arteriole.…”

Section: Introductionmentioning

confidence: 99%

3D network model of NO transport in tissue

Chen

Buerk

Barbee

et al. 2011

Med Biol Eng Comput

Self Cite

View full text Add to dashboard Cite

We developed a mathematical model to simulate shear stress-dependent nitric oxide (NO) production and transport in a 3D microcirculatory network based on published data. The model consists of a 100 μm × 500 μm × 75 μm rectangular volume of tissue containing two arteriole-branching trees, and nine capillaries surrounding the vessels. Computed distributions for NO in blood, vascular walls, and surrounding tissue were affected by hematocrit (Hct) and wall shear stress (WSS) in the network. The model demonstrates that variations in the red blood cell (RBC) distribution and WSS in a branching network can have differential effects on computed NO concentrations due to NO consumption by RBCs and WSS-dependent changes in NO production. The model predicts heterogeneous distributions of WSS in the network. Vessel branches with unequal blood flow rates gave rise to a range of WSS values and therefore NO production rates. Despite increased NO production in a branch with higher blood flow and WSS, vascular wall NO was predicted to be lower due to greater NO consumption in blood, since the microvascular Hct increased with redistribution of RBCs at the vessel bifurcation. Within other regions, low WSS was combined with decreased NO consumption to enhance the NO concentration.

show abstract

“…In our model, we used 45% as the physiological hematocrit [20,21], which means that the area occupied by the erythrocytes in the lumen accounts for 45% of the total luminal cross-section. Our model also recognizes that the in vivo vessel hematocrit in arterioles may be significantly smaller than 45%, corresponding to the systemic hematocrit [22].…”

Section: Model Geometry and Assumptionsmentioning

confidence: 99%

Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes

et al. 2008

View full text Add to dashboard Cite

Experimental evidence has shown that nitrite anion plays a key role in one of the proposed mechanisms for hypoxic vasodilation, in which the erythrocyte acts as a NO generator and deoxygenated hemoglobin in pre-capillary arterioles reduces nitrite to NO, which contributes to vascular smooth muscle relaxation. However, because of the complex reactions among nitrite, hemoglobin, and the NO that is formed, the amount of NO delivered by this mechanism under various conditions has not been quantified experimentally. Furthermore, paracrine NO is scavenged by cellfree hemoglobin, as shown by studies of diseases characterized by extensive hemolysis (e.g., sickle cell disease) and the administration of hemoglobin-based oxygen carriers. Taking into consideration the free access of cell-free hemoglobin to the vascular wall and its ability to act as a nitrite reductase, we have now examined the hypothesis that in hypoxia this cell-free hemoglobin could serve as an additional endocrine source of NO. In this study, we constructed a multicellular model to characterize the amount of NO delivered by the reaction of nitrite with both intraerythrocytic and cell-free hemoglobin, while intentionally neglecting all other possible sources of NO in the vasculature. We also examined the roles of hemoglobin molecules in each compartment as nitrite reductases and NO scavengers using the model. Our calculations show that: (1) ~0.04 pM NO from erythrocytes could reach the smooth muscle if free diffusion were the sole export mechanism; however, this value could rise to ~43 pM with a membrane-associated mechanism that facilitated NO release from erythrocytes; the results also strongly depend on the erythrocyte membrane permeability to NO; (2) despite the closer proximity of cell-free hemoglobin to the smooth muscle, cell-free hemoglobin reaction with nitrite generates approximately 0.02 pM of free NO that can reach the vascular wall, because of a strong self-capture effect. However, it is worth noting that this value is in the same range as erythrocytic hemoglobin-generated NO that is able to diffuse freely out of the cell, despite the tremendous difference in hemoglobin concentration in both cases (μM hemoglobin in plasma vs. mM in erythrocyte); (3) intraerythrocytic hemoglobin encapsulated by a NO-resistant membrane is the major source of NO from nitrite reduction, and cell-free hemoglobin is a significant scavenger of both paracrine and endocrine NO.* Corresponding

show abstract

A Model of NO/O2 Transport in Capillary-perfused Tissue Containing an Arteriole and Venule Pair

Cited by 48 publications

References 43 publications

Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective

Nitric Oxide in the Vasculature: Where Does It Come From and Where Does It Go? A Quantitative Perspective

3D network model of NO transport in tissue

Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytes

Contact Info

Product

Resources

About