Abstract 15878: Pulse Pressure and Intraluminal Mean Pressure Regulate Endothelium-Dependent Flow-Mediated Dilation in Cerebral Arteries of Dyslipidemic Mice
Introduction: In vivo, resting arterial blood pressure in cerebral arteries is pulsatile; however, whether pulse pressure (PP) regulates endothelial shear stress (SS) sensitivity is unknown. The aim of this study was to design a computer-controlled pneumatic system mounted in series with a small vessel pressure myograph generating a PP to test its impact on endothelium-dependent flow-mediated dilatation (FMD) in cerebral arteries from C57Bl/6J (WT) mice and dyslipidemic (LDLR-/-;hApoB+/+, ATX) 3-mo mice.
Methods: Isolated posterior cerebral arteries (n=10 per group) were pressurized at a mean physiological (60 mm Hg) or high (80 mm Hg) pressure either in static (SP) or PP condition of ±15 mm Hg, at a rate of 550 pulses per minute mimicking resting heart rate in conscious mice. Varying SS (2 to 20 dyn/cm2) was applied to pre-constricted vessels and endothelial sensitivity was assessed by measuring FMD (% of max diameter).
Results: In arteries isolated from WT mice, FMD was similar in SP and PP conditions for SS up to 15 dyn/cm2. However, starting at 20 dyn/cm2, PP increased FMD (Table). In contrast, at a pressure of 80 mm Hg, FMD (20 dyn/cm2) were reduced, however more in PP than in SP condition. In both SP and PP conditions, cerebral arteries did not dilate (p<0.001) after eNOS inhibition (L-NNA, 100 μM) or endothelial denudation. Finally, ATX mice displayed endothelial dysfunction (Table); yet, PP increased FMD at 60 mm Hg. However, at 80 mm Hg, FMD was unaffected by PP and similar to WT.
Conclusion: Endothelial SS sensitivity is sensitive to the intraluminal pressure and is regulated by PP, even in the presence of a dysfunctional endothelium.
Author Disclosures: A. Raignault: None. V. Bolduc: None. F. Lesage: None. E. Thorin: None.
- © 2014 by American Heart Association, Inc.