Pulse Pressure Reveals Shear Stress-Dependent Enos Activity In Mice Cerebral Arteries

Introduction While in vivo arterial blood pressure in cerebral arteries is oscillatory and pulsated, in vitro cerebral arterial function is assessed under a static pressure. Thus, whether pulse pressure (PP) regulates cerebral endothelial shear stress (SS) sensitivity and myogenic tone (MT) is unknown. The aim of this study was to test in vitro the impact of PP on MT and eNOS-dependent flow-mediated dilation (FMD) in mouse cerebral arteries. Methods. Using a custom computer-controlled pneumatic system generating a PP (used at ±15 mm Hg, rate of 550 pulses per minute), isolated posterior cerebral arteries from 3-month old C57Bl/6J mice (n=10) were pressurized at 60 mm Hg, either in static or PP conditions. SS from 2 to 20 dyn/cm2 were applied and FMD measured. Arteries were incubated with or without L-NNA (100 µM; eNOS inhibitor) or PEG-catalase (100 U/ml). Results. Without PP, MT was low but potentiated by both L-NNA and PEG-catalase (p<0.05). PP significantly increased MT (p<0.05), independently of L-NNA and PEG-catalase, suggesting that PP inhibits eNOS activity. In both static and PP conditions, cerebral arteries did not dilate to SS in the presence of L-NNA or after endothelial denudation (p<0.001). Up to 15 dyn/cm2, SS elicited similar FMD in static and PP conditions; at 20 dyn/cm2, however, FMD were higher in the presence of PP (p<0.05). PEG-catalase reduced (p<0.05) FMD in static but not in PP, suggesting that PP promotes eNOS-derived NO pathway. Conclusion PP modulates cerebrovascular eNOS activity: at rest, PP inhibits eNOS, increasing MT. In the presence of flow, PP reveals SS-dependent eNOS-derived NO release, leading to higher FMD.