Interactions between NO and O2 in the microcirculation: a mathematical analysis

Biotransport of nitric oxide (NO) and of oxygen (O(2)) in the microcirculation are inherently interdependent, since all nitric oxide synthase (NOS) isoforms (eNOS, nNOS, and iNOS) require O(2) to produce NO. Furthermore, tissue O(2) consumption is reversibly inhibited by NO. To investigate these complex interactions, a mathematical model was developed for coupled mass transport of NO and O(2) around a cylindrical arteriole using finite element computational methods. Steady-state radial NO and O(2) gradients in the bloodstream, plasma layer, endothelium, vascular wall, and surrounding tissue were simulated for different conditions. Special cases of the model were solved, including O(2)-dependent NO production from eNOS alone, and with additional NO production from either nNOS or iNOS at specified locations. The model predicts that (a) concentration changes in one species can have significant effects on transport of the other species with the degree of interaction dependent on spatial gradients; (b) eNOS NO production rates required to maintain the concentration of NO in the vascular wall are more dependent on NO scavenging in blood than in tissue; (c) relatively low rates of NO production in tissue from either nNOS or iNOS can elevate vascular wall NO, compensating for possible reductions in NO production from eNOS; (d) depending on their physical location, nNOS and iNOS can be very sensitive to O(2); and (e) increased tissue NO can increase O(2) delivery to more distal regions by inhibiting O(2) consumption in other regions.