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.