Abstract
A plasma stratum (cell free layer or CFL) generated by flowing blood interposed between the red blood cell (RBC) core and the endothelium affects generation, consumption, and transport of nitric oxide (NO) in the microcirculation. CFL width is a principal factor modulating NO diffusion and vessel wall shears stress development, thus significantly affecting NO bioavailability. Since the CFL is bounded by the surface formed by the chaotically moving RBCs and the stationary but spatially non-uniform endothelial surface, its width fluctuates randomly in time and space. We analyze how these stochastic fluctuations affect NO transport in the CFL and NO bioavailability. We show that effects due to random boundaries do not average to zero and lead to an increase of NO bioavailability. Since endothelial production of NO is significantly enhanced by temporal variability of wall shear stress, we posit that stochastic shear stress stimulation of the endothelium yields the baseline continual production of NO by the endothelium. The proposed stochastic formulation captures the natural continuous and microscopic variability, whose amplitude is measurable and is of the scale of cellular dimensions. It provides a realistic model of NO generation and regulation.
Highlights
Nitric oxide (NO) plays a critical role in the local control of smooth muscle tone and the regulation of blood flow at the microvascular level
The local concentration of NO in blood results from the competition between NO diffusing from the endothelium and NO scavenging by hemoglobin in red blood cells (RBCs) or at times dissolved in plasma
We developed a computational framework to quantify the impact of spatio-temporal fluctuations in the cell free layer (CFL) width on the production and transport of NO
Summary
Nitric oxide (NO) plays a critical role in the local control of smooth muscle tone and the regulation of blood flow at the microvascular level. Mathematical modeling was used (Vaughn et al, 1998a,b; Condorelli and George, 2002; Kavdia and Popel, 2003; Lamkin-Kennard et al, 2004; Chen et al, 2006; Ong et al, 2011b; Sriram et al, 2011) to determine the NO distribution in blood vessels simulated by cylindrical and parallelplate compartments, as a function of local transport parameters such as NO production rate, scavenging reaction rate and diffusion coefficients in blood and tissue. Mechanotransduction generates a significant portion of the NO involved in the regulation of blood flow (Condorelli and George, 2002; Chen et al, 2006) This mechanical effector links the biochemistry of NO production by the endothelium with shear stress induced by blood flow on the vascular wall (WSS). This coupling is tight because NO bioavailability in the vascular
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