Effects of cell-free layer formation on NO/O2 bioavailability in small arterioles.

We developed a new time-dependent computational model for coupled NO/O(2) transport in small arterioles that incorporates potential physiological responses (temporal changes in NO scavenging rate and O(2) partial pressure in blood lumen and NO production rate in endothelium) to the temporal cell-free layer width variations. Two relations between wall shear stress (WSS) and NO production rate based on the linear and sigmoidal functions were considered in this simulation study. The cell-free layer data used for the simulation were acquired from arteriolar flows (D=48.3 ± 1.9 µm) in the rat cremaster muscles under normal flow conditions (WSS=3.4-5.6 Pa). For both cases of linear and sigmoidal relations, temporal layer width variations were found to be capable of significantly enhancing NO bioavailability and this effect was more pronounced in the latter (P<0.0005) than the former (P<0.005). In contrast, O(2) bioavailability in the arteriolar wall was not considerably altered by the temporal layer width variations, irrespective of the relation. Prominent enhancement (P<0.005) of soluble guanylyl cyclase (sGC) activation in the smooth muscle by the temporal layer width variations were predicted for both relations. The extent of sGC activation was generally lower (P<0.01) in the case of the sigmoidal relation than that of the linear relation, suggesting a lesser tendency for arterioles to dilate with the former.