How abundant are superoxide and hydrogen peroxide in the vasculature lumen, how far can they reach?

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.