A computational model for free radicals transport in the microcirculation.
Nitric oxide (NO), superoxide (O(2)(-)), and peroxynitrite (ONOO(-)) interactions in pathophysiologic conditions such as cardiovascular disease, hypertension, and diabetes have been studied extensively in vivo and in vitro. A reduction in bioavailability of NO is a common event that is known as the endothelial dysfunction in these conditions. Despite intense investigation of NO biotransport and O(2)(-) and ONOO(-) biochemical interactions in vasculature, we have very little quantitative knowledge of distributions and concentrations of NO, O(2)(-), and ONOO(-) under normal physiologic and pathophysiologic conditions. Based on fundamental principles of mass balance, vessel geometry, and reaction kinetics, we developed a mathematical model of these free radicals transport in and around an arteriole during oxidative stress. We investigated the role of O(2)(-) and ONOO(-) in inactivating vasoactive NO. The model predictions include (a) NO interactions with oxygen, O(2)(-), and ONOO(-) have relatively little effect on the NO level in the vascular smooth muscle under physiologic conditions; (b) superoxide diffuses only a few microns from its source, whereas peroxynitrite diffuses over a larger distance; and (c) reduced superoxide dismutase levels significantly increase O(2)(-) and peroxynitrite concentrations and decrease NO concentration. Model results indicate that the reduced NO bioavailability and enhanced peroxynitrite formation may vary depending on the location of oxidative stress in the microcirculation, which occurs at diverse vascular cell locations in diabetes, aging, and cardiovascular diseases. The results will have significant implications for our understanding of these free radical interactions in physiologic and pathophysiologic conditions resulting from endothelial dysfunction.
Kavdia
Mahendra
M
Biomedical Engineering Program, University of Arkansas, Fayetteville, 72701, USA. mkavdia@uark.edu
D001160:Arterioles / Q000378:metabolism; D001682:Biological Availability; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003198:Computer Simulation; D003920:Diabetes Mellitus / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology; D007700:Kinetics; D008833:Microcirculation; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D010100:Oxygen