Temporal variations of the cell-free layer width may enhance NO bioavailability in small arterioles: Effects of erythrocyte aggregation

Recently, we have shown that temporal variations in the cell-free layer width can potentially enhance nitric oxide (NO) bioavailability in small arterioles. Since the layer width variations can be augmented by red blood cell aggregation, we tested the hypothesis that an increase in the layer width variations due to red blood cell aggregation could provide an underlying mechanism to improve NO bioavailability in the endothelium and promote vasodilatory effects. Utilizing cell-free layer width data acquired from arterioles of the rat cremaster muscle before and after dextran infusion in reduced flow conditions (wall shear stress=0.13-0.24Pa), our computational model predicted exponential enhancements of NO bioavailability in the endothelium and soluble guanylyl cyclase (sGC) activation in the smooth muscle layer with increasing temporal variability of the layer width. These effects were mediated primarily by the transient responses of wall shear stress and NO production rate to the layer width variations. The temporal variations in the layer width were significantly enhanced (P<0.05) by aggregation, leading to significant improvements (P<0.05) in NO bioavailability and sGC activation. As a result, the significant reduction (P<0.05) of sGC activation due to the increased width of the layer after aggregation induction was diminished by the opposing effect of the layer variations. These findings highlighted the possible enhancement of NO bioavailability and vascular tone in the arteriole by the augmented layer width variations due to the aggregation.