A model of nitric oxide capillary exchange.

Abstract

Our aim was to develop a mathematical model that describes the nitric oxide (NO) transport in and around capillaries. The model is used to make quantitative predictions for (1) the contribution of capillary endothelium to the nitric oxide flux into the parenchymal tissue cells; (2) the scavenging of arteriolar endothelium-derived NO by capillaries in the surrounding tissue; and (3) the role of myoglobin in tissue cells and plasma-based hemoglobin on NO diffusion in and around capillaries. We used a finite element model of a capillary and surrounding tissue with discrete parachute-shape red blood cells (RBCs) moving inside the capillary to obtain the NO concentration distribution. An intravascular mass transfer coefficient is estimated as a function of RBC membrane permeability and capillary hematocrit. A continuum model of the capillary is also formulated, in which blood is treated as a homogeneous fluid; it uses the mass transfer coefficient and provides a closed-form analytic solution for the average exchange rate of NO in a capillary-perfused region. The NO concentration in the parenchymal cells depends on parameters such as RBC membrane permeability and capillary hematocrit; the concentration is predicted for a wide range of parameters. In the absence of myoglobin or plasma-based hemoglobin, the average tissue concentration generally ranges between 20 and 300 nM. In the presence of myoglobin or after transfusion of a hemoglobin-based blood substitute, there is minimal NO penetration into the tissue from the capillary endothelium. The model suggests that NO originating from the capillary wall can diffuse toward the parenchymal cells and potentially sustain physiologically significant concentrations. The model provides estimates of NO exchange and concentration level in capillary-perfused tissue, and it can be used in models of NO transport around arterioles or other NO sources.