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Purpose: In this study, we examined whether the decrease in endothelial function associated with short-term exposure to elevated retrograde shear rate (SR), could be prevented when combined with a concurrent drop in transmural pressure in humans. Methods: Twenty-five healthy individuals reported to our laboratory on three occasions to complete 30-min experimental conditions, preceded and followed by assessment of endothelial function using flow-mediated dilation (FMD). We used cuff inflation for 30-min to manipulate retrograde SR and transmural pressure in the brachial artery. Subjects underwent, in randomised order: (1) forearm cuff inflation to 60 mmHg (distal cuff; causing increase in retrograde SR), (2) upper arm cuff inflation to 60 mmHg (proximal cuff; causing increase in retrograde SR + decrease in transmural pressure), and (3) no cuff inflation (Control). Results: The distal and proximal cuff conditions both increased brachial artery retrograde SR (p < 0.001) and oscillatory shear index (p < 0.001). The Control intervention did not alter SR patterns or FMD (p > 0.05). A significant interaction-effect was found for FMD (p < 0.05), with the decrease during distal cuff (from 6.9 ± 2.3% to 6.1 ± 2.5%), being reversed to an increase with proximal cuff (from 6.3 ± 2.0 to 6.9 ± 2.0%). The proximal cuff-related increase in FMD could not be explained by the decrease in antegrade or increase in retrograde shear. Conclusion: This study suggests that a decrease in transmural pressure may ameliorate the decline in endothelial function that occurs following exposure to elevated retrograde shear in healthy individuals.
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