Nitric oxide (NO) produced by endothelial cells is a key component for blood-vessel dilation. Dilation is achieved through smooth muscle relaxation as a response to NO transport. Inhibition of this process occurs through the inactivation of NO by reactive oxygen species, especially superoxide (O2 -). NO and superoxide react quickly, forming peroxynitrite (ONOO-). Both superoxide and peroxynitrite apply oxidative stress on vascular tissue. Experimental studies investigating NO interactions are difficult since these reactions occur rapidly and over small distances. This study presents a computational model to describe the interactions of NO, superoxide, and peroxynitrite across an arteriole/venule pair. Based on principles of mass transport, and using knowledge of chemical concentrations and reaction rates, a mathematical model was developed to generate the concentration profiles for NO, O2 -, and ONOO-. We simulated excessive oxidative stress by uncoupled eNOS and determined its effect on NO concentration profiles throughout the region. Based on our understanding of the interactions involved, we predicted 1) increased oxidative stress in the venule decreases NO levels in regions of both the venule and neighboring arteriole, and 2) the amount of NO reduction will vary depending on the location of O2 - increase. The model demonstrates that different sources of O2 - have varied effects on NO concentration profiles, and excessive oxidative stress in the venule can impact NO levels in the venule as well as the arteriole. The results provide a more complete description of nitric oxide transfer, which is an important step toward understanding vascular complications in many pathological conditions.
Richardson, William and Kavdia, Mahendra
"A computational model for analysis of uncoupled NO synthase on nitric oxide and superoxide interaction in microcirculation,"
Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences. University of Arkansas System Division of Agriculture. 8:67-76.
Available at: http://scholarworks.uark.edu/discoverymag/vol8/iss1/12