Stimulus-response specificity of human conduit artery flow mediated dilation

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Pyke, Kyra Ellen, 1977-
Endothelial function , Flow mediated dilation
An increase in blood flow associated shear stress results in an endothelial dependent increase in vessel diameter (flow mediated vasodilation (FMD)). Assessment of FMD can provide an index of endothelial function. The stimulus profiles that have been used to investigate FMD in human conduit arteries fall into two categories: reactive hyperemia and sustained stimuli. Stimulus-response specificity proposes that the stimulus characteristics (e.g. magnitude, pattern) are essential determinants of the response characteristics (e.g. magnitude, mechanisms). Purpose: To investigate four specific aspects of FMD stimulus-response specificity: 1) The relative importance of the peak vs. the duration of reactive hyperemia in determining FMD response magnitude. 2) The nitric oxide (NO) dependence of FMD following different durations of reactive hyperemia. 3) The impact of sustained shear stress stimulus magnitude on FMD response dynamics and magnitude. 4) FMD dynamics and magnitude in response to steady vs. oscillatory shear stress evoked passively or via exercise. Methods: Doppler ultrasound was applied to the brachial or radial artery to measure blood flow velocity. Vessel diameter was measured with automated edge detection software. Shear rate, an estimate of shear stress was calculated as the blood flow velocity/vessel diameter. Results: 1) The duration of reactive hyperemia is an important determinant of peak FMD magnitude while the independent contribution of the peak shear to FMD is minimal. 2) NO is not obligatory to FMD following either a five or a ten minute duration occlusion. 3) FMD in response to a sustained stimulus is characterized by a generally bi-phasic response with a fast first phase followed by a slower final phase. 4) The endothelium transduces the mean shear stress when it is exposed passive or handgrip exercise induced oscillations in shear stress. Conclusions: The results indicate that future reactive hyperemia studies must account for the stimulus duration when interpreting FMD results. Further, they demonstrate that the role of NO in FMD is unclear and caution against oversimplified conceptual models of FMD mechanisms. FMD in response to sustained stimuli provides information distinct from reactive hyperemia investigations and exercise may provide a valuable stimulus creation technique.
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