Pulse pressure oscillations regulate cerebrovascular reactivity to flow (1070.5)

Abstract

In vivo, arterial blood pressure is oscillatory and pulsated. This pulse pressure (PP) corresponds to the difference between the systolic and diastolic pressure, and its frequency is dictated by heart rate (bpm). Our aim was to determine, in vitro, the unknown impact of PP (30 mm Hg, 550 bpm) on endothelial shear stress sensitivity (flow‐mediated dilatation) of mouse cerebral arteries. Methods/results: We developed an original system that generates a pulse‐wave adjustable in amplitude and frequency, and can be connected to a pressure arteriograph. Middle cerebral arteries (≍160 µm diameter, n=10 per group) were isolated from 3‐month old C57Bl6 mice and pressurized at 60 or 100 mm Hg either in static pressure (SP) or PP conditions. At 60 mm Hg, pre‐constricted arteries similarly dilated to an increase in flow up to a shear stress of 15 dyn/cm2, to 59±6% of the maximal diameter in PP, and 52±10% in SP conditions. In response to a higher shear stress of 20 dyn/cm2, however, arteries further dilated in PP (73±7%; p<0.05) unlike in SP (43±9%) conditions. At 100 mm Hg, arteries dilated in response to low shear stress (8 dyn/cm2) but less at high shear stresses (20 dyn/cm2): dilation was reduced by 50% in SP (from 44±11% to 23±11%; p<0.05) and 75% in PP (from 34±3% to 8±4%; p<0.05) conditions. Conclusion: PP increases the sensitivity of the endothelium to shear stress at physiological pressure (60 mm Hg) while it limits its sensitivity to high shear stress at high pressure (100 mm Hg), suggesting that PP regulates the endothelial function to critically adjust vessel diameter and flow to neuronal metabolic demand.Grant Funding Source: CIHR