How abundant are superoxide and hydrogen peroxide in the vasculature lumen, how far can they reach?
Tânia Sousa, Marcos Gouveia, Rui D. M. Travasso, Armindo Salvador
Abstract
Paracrine superoxide (O2•−) and hydrogen peroxide (H2O2) signaling critically depends on these substances' concentrations, half-lives and transport ranges in extracellular media. Here we estimated these parameters for the lumen of human capillaries, arterioles and arteries using reaction-diffusion-advection models. These models considered O2•− and H2O2 production by endothelial cells and uptake by erythrocytes and endothelial cells, O2•− dismutation, O2•− and H2O2 diffusion and advection by the blood flow. Results show that in this environment O2•− and H2O2 have half-lives <60. ms and <40. ms, respectively, the former determined by the plasma SOD3 activity, the latter by clearance by endothelial cells and erythrocytes. H2O2 concentrations do not exceed the 10 nM scale. Maximal O2•− concentrations near vessel walls exceed H2O2's several-fold when the latter results solely from O2•− dismutation. Cytosolic dismutation of inflowing O2•− may thus significantly contribute to H2O2 delivery to cells. O2•− concentrations near vessel walls decay to 50% of maximum 12 μm downstream from O2•− production sites. H2O2 concentrations in capillaries decay to 50% of maximum 22 μm (6.0 μm) downstream from O2•− (H2O2) production sites. Near arterioles' (arteries') walls, they decay by 50% within 6.0 μm (4. μm) of H2O2 production sites. However, they reach maximal values 50 μm (24 μm) downstream from O2•− production sites and decrease by 50% over 650 μm (500 μm). Arterial/olar endothelial cells might thus signal over a mm downstream through O2•−-derived H2O2, though this requires nM-sensitive H2O2 transduction mechanisms.