Endothelial cell dilatory pathways link flow and wall shear stress in an intact arteriolar network

Our purpose was to determine whether the endothelial cell-dependent dilatory pathways contribute to the regulation of flow distribution in an intact arteriolar network. Cell flow, wall shear stress (T-omega), diameter, and bifurcation angle were determined for four sequential branches of a transverse arteriole in the superfused cremaster muscle of pentobaribtal sodium (Nembutal, 70 mg/kg)-anesthetized hamsters (n = 51). Control cell flow was significantly greater into upstream than into downstream branches [1,561 +/- 315 vs. 971 +/- 200 (SE) cells/s, n = 12]. Tissue exposure to 50 mu M N-omega-nitro-L-arginine + 50 mu M indomethacin (L-NNA + Indo) produced arteriolar constriction of 14 +/- 4% and decreased flow into the transverse arteriole. More of the available cell flow was diverted to downstream branches, yet flow distribution remained unequal. Control T-omega was higher upstream than downstream (31.3 +/- 6.8 vs. 9.8 +/- 1.5 dyn/cm2). L-NNA + Indo decreased T-omega upstream and increased T-omega downstream to become equal in all branches, in contrast to flow. To determine whether constriction in general induced the same changes, 5% O-2 (8 +/- 4% constriction) or 10(-9) M norepinephrine (NE; 4 +/- 3% constriction) was added to the tissue (n = 7). With O-2, flow was redistributed to become equal into each branch. With NE, flow decreased progressively more into the first three branches. The changes in flow distribution were thus predictable and dependent on the agonist. With O-2 or NE, the spatial changes in flow were mirrored by spatial changes in T-omega. Changes in diameter and in cell flux were not related for L-NNA + Indo (r = 0.45), O-2 (r = 0.07), or NE (r = 0.36). For all agonists, when the bifurcation angle increased, cell flow to the branch decreased significantly, whereas if the angle decreased, flow was relatively preserved; thus active changes in bifurcation angle may influence red cell distribution at arteriolar bifurcations. Thus, when the endothelial cell dilatory pathways were blocked, the changes in flow and in T-omega were uncoupled; yet when they were intact, flow and T-omega changed together.