Estimation of nitric oxide production and reaction rates in tissue by use of a mathematical model

Nitric oxide (NO) produced by the vascular endothelium is an important biologic messenger that regulates vessel tone and permeability and inhibits platelet adhesion and aggregation. NO exerts its control of vessel tone by interacting with guanylyl cyclase in the vascular smooth muscle to initiate a series of reactions that lead to vessel dilation. Previous efforts to investigate this interaction by mathematical modeling of NO diffusion and reaction have been hampered by the lack of information on the production and degradation rate of NO. We use a mathematical model and previously published experimental data to estimate the rate of NO production, 6.8 x 10(-14) mu mol.mu m(-2).s(-1); the NO diffusion coefficient, 3,300 mu m(2) s(-1); and the NO consumption rate coefficient in the vascular smooth muscle, 0.01 s(-1) (Ist-order rate expression) or 0.05 mu M-1.s(-1) (2nd-order rate expression). The modeling approach is discussed in detail. It provides a general framework for modeling the NO produced from the endothelium and for estimating relevant physical parameters.