3D network model of NO transport in tissue

Abstract

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.

Nitric oxide transport in an axisymmetric stenosis

“…The first one was based on (2.12). The second was assumed to have an R NO that was linearly dependent on WSS as described by [20] Figure 6 shows the distribution of NO concentration at the lumen-wall interface and at the media-adventitia interface. When compared with simulations based on R NO -hyp in (2.12), owing to the much higher NO production rate, the NO concentration obtained for R NO -linear is much higher.…”

Another role for nitric oxide in blood flow control?

“…In this current issue, Chen et al [7] proposes another flow control mechanism that contributes to local redistribution of blood flow by diameter control of the precapillary arterioles (\30 lm). They developed a mathematical model to investigate NO diffusion in tissue (notably to the vascular smooth muscle cells) perfused by a small reconstructed microvascular network of the hamster cheek pouch retractor muscle.…”

A mathematical model for the role of N 2 O 3 in enhancing nitric oxide bioavailability following nitrite infusion

“…2) as in our previous model [26] in order to determine if the NO response to nitrite infusion changed with different flow rates. Blood flow changes of 20% to the baseline centerline velocity of 1000 μm s −1 significantly changes SMC NO from shear-dependent eNOS (Fig.…”

“…Mass transport models for NO transport have been constructed and reviewed previously [25,26], and the approach here is similar to theirs. NO production ( R NO ) was assumed to be uniform and confined to endothelial NOS (layer 3).…”

“…2) with all other substrates and co-factors present in abundance. $$R_{NO}=R_{N{O}_{\mathit{\text{max}}}}\left(\frac{P_{O_2}}{P_{O_2}+K_m}\right)\left(\frac{{\tau }_w}{{\tau }_{\mathit{\text{ref}}}}\right)$$ where K m is the Michaelis-Menten constant, and τ ref is the reference value used by Chen et al [26]. $R_{{\text{NO}}_{\text{max}}}$ was chosen so that at baseline flow, R NO matches the purely O 2 -dependent Michaelis-Menten values used by Buerk [25].…”