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

Paracrine superoxide (O(2)(•−)) and hydrogen peroxide (H(2)O(2)) 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 O(2)(•−) and H(2)O(2) production by endothelial cells and uptake by erythrocytes and endothelial cells, O(2)(•−) dismutation, O(2)(•−) and H(2)O(2) diffusion and advection by the blood flow. Results show that in this environment O(2)(•−) and H(2)O(2) 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. H(2)O(2) concentrations do not exceed the 10 nM scale. Maximal O(2)(•−) concentrations near vessel walls exceed H(2)O(2)'s several-fold when the latter results solely from O(2)(•−) dismutation. Cytosolic dismutation of inflowing O(2)(•−) may thus significantly contribute to H(2)O(2) delivery to cells. O(2)(•−) concentrations near vessel walls decay to 50% of maximum 12 μm downstream from O(2)(•−) production sites. H(2)O(2) concentrations in capillaries decay to 50% of maximum 22 μm (6.0 μm) downstream from O(2)(•−) (H(2)O(2)) production sites. Near arterioles' (arteries') walls, they decay by 50% within 6.0 μm (4. μm) of H(2)O(2) production sites. However, they reach maximal values 50 μm (24 μm) downstream from O(2)(•−) production sites and decrease by 50% over 650 μm (500 μm). Arterial/olar endothelial cells might thus signal over a mm downstream through O(2)(•−)-derived H(2)O(2), though this requires nM-sensitive H(2)O(2) transduction mechanisms.