Impact of intermittent elevations in shear rate on peripheral endothelial function
Creators: name: Hanson, Brady E.
Publisher: name: University of Iowa
Year: 2025
Subjects: Intermittent Exercise
Intermittent Hypoxia
Peripheral Endothelial Function
Shear Rate
public abstract

description: The ability of arteries to appropriately dilate is an important physiological function in mediating blood flow throughout the body. The vascular endothelium plays a key role in regulating blood flow through the balance of vasodilation and vasoconstriction. This regulatory process is termed endothelial function. Impairments to this process, or endothelial dysfunction, can have adverse effects throughout the body. Many diseases such as diabetes, various cancers, and most notably atherosclerosis and cardiovascular disease can all be linked to endothelial dysfunction. As cardiovascular diseases are among the leading causes of death in the United States and throughout the world, understanding ways to improve endothelial function will aid in the prevention and treatment of such diseases.
description: The vascular system is heavily influenced by many hemodynamic forces, with shear stress being of great importance. Shear stress is the frictional force created by blood flowing across the endothelial lining of vessels. Increases in blood flow and subsequently shear stress, or shear rate (SR), stimulate the endothelium to release vasoactive substances which control vascular tone through constriction and dilation. One such substance is the potent vasodilator nitric oxide, widely understood as a crucial component to endothelial function. Increased SR can be accomplished by a number of methods including exercise, heating, and hypoxia exposure. Many preclinical and translational studies have indicated the importance of increased SR as a stimulus for vasodilation and eliciting vascular adaptations. Sustained increases in SR has been well documented as playing a significant role in improving measures of peripheral endothelial function. Recent evidence suggest altering the pattern of SR in a cyclic intermittent manner (i.e., periods of increased SR followed by periods of lower SR) may represent a more effective method of improving endothelial function, however this concept has not been fully explored. The objective of this research was to examine if intermittent elevations in SR, elicited by various methods, can improve endothelial function to a greater extent compared to sustained elevations.
description: The main objective of the research presented in Chapter 2 was to determine if 50 min of intermittent hypoxia exposure has a more beneficial impact compared to continuous hypoxia on peripheral endothelial function as assessed by flow-mediated dilation (FMD). Intermittent hypoxia was administered for 6 min intervals separated by 4 min of normoxia. SR increased during each hypoxic interval and returned towards baseline levels during normoxia. During continuous hypoxia exposure, SR remained elevated with no interruption across the entire intervention. Findings from this study indicate that both intermittent and continuous hypoxia were able to offset the decline in FMD following inactivity, supporting the notion that increasing SR is beneficial to endothelial function. Interestingly, when FMD was normalized to the shear stimulus, only intermittent hypoxia improved FMD. Collectively, these findings suggest hypoxia-induced elevations in SR can offset the deleterious effect of inactivity.
description: Chapter 3 explored the impact of intermittent and continuous handgrip exercise on improving endothelial function. Three different rhythmic forearm exercise interventions were performed. Intermittent exercises (6 bouts of 3 min exercise interspersed with 2 min of rest) were performed at 25% (INT-25%) and 15% (INT-15%) maximum voluntary contraction (MVC), and continuous exercise was completed at 15% MVC. The total SR during exercise increased in all three trials, with INT-25% and continuous increasing significantly more than INT-15%. FMD was also increased following all trials, with the greatest increase following INT-25% compared to INT-15% and continuous. Further, when FMD was normalized to the shear stimulus, both intermittent exercises increased to a greater degree than continuous exercise. Interestingly, a mixed model linear regression confirms that the impact of intermittent exercise was more influential than continuous exercise on improving FMD. Overall, these findings indicate that intermittent exercise and the resultant intermittent fluctuations in SR acutely improve peripheral endothelial function more so than continuous exercise.
description: Collectively, this research supports our original hypothesis that intermittent elevations in SR have a greater effect on acutely improving peripheral endothelial function compared to sustained elevations. While elevations in SR, as well as the magnitude of increase, is a significant stimulus for improvements we found that the pattern of administration is also important and may be potentially more influential.