Mathematical model for shear stress dependent NO and adenine nucleotide production from endothelial cells

We developed a mass transport model for a parallel-plate flow chamber apparatus to predict the concentrations of nitric oxide (NO) and adenine nucleotides (ATP, ADP) produced by cultured endothelial cells (ECs) and investigated how the net rates of production, degradation, and mass transport for these three chemical species vary with changes in wall shear stress (tau(W)). These simulations provide an improved understanding of experimental results obtained with parallel-plate flow chambers and allows quantitative analysis of the relationship between tau(W), adenine nucleotide concentrations, and NO produced by ECs. Experimental data obtained after altering ATP and ADP concentrations with apyrase were analyzed to quantify changes in the rate of NO production (R-NO). The effects of different isoforms of apyrase on ATP and ADP concentrations and nucleotide-dependent changes in R-NO could be predicted with the model. A decrease in ATP was predicted with apyrase, but an increase in ADP was simulated due to degradation of ATP. We found that a simple proportional relationship relating a component of R-NO to the sum of ATP and ADP provided a close match to the fitted curve for experimentally measured changes in R-NO with apyrase. Estimates for the proportionality constant ranged from 0.0067 to 0.0321 mu M/s increase in R-NO per nM nucleotide concentration, depending on which isoform of apyrase was modeled, with the largest effect of nucleotides on R-NO at low tau(W) (<6 dyn/cm(2)). (C) 2015 Elsevier Inc. All rights reserved.