Vascular smooth muscle NO exposure from intraerythrocytic SNOHb: a mathematical model

We previously constructed computational models based on the biochemical pathway analysis of different nitric oxide (NO) synthase isoforms and found a large discrepancy between our predictions and perivascular NO measurements, suggesting the existence of nonenzymatic sources of NO. S-nitrosohemoglobin (SNOHb) has been suggested as a major source to release NO in the arteriolar lumen and induce hypoxic vasodilation. In the present study, we formulated a multicellular computational model to quantify NO exposure in arteriolar smooth muscle when the NO released by intraerythrocytic SNOHb is the sole NO source in the vasculature. Our calculations show an NO exposure of approximately 0.25-6 pM in the smooth muscle region. This amount does not account for the large discrepancy we encountered regarding perivascular NO levels. We also found that the amount of NO delivered by SNOHb to smooth muscle strongly depends on the SNOHb concentration and half-life, which further determine the rate of NO release, as well as on the membrane permeability of red blood cells (RBCs) to NO. In conclusion, our mathematical model predicts that picomolar amounts of NO can be delivered to the vascular smooth muscle by intraerythrocytic SNOHb; this amount of NO alone appears not sufficient to induce the hypoxic vasodilation.