Peripheral artery endothelial function responses to altered blood flow in humans

Abstract

Endothelial function is influenced by a variety of factors, including shear stress direction and magnitude. Whereas improvements in endothelial function have mostly been attributed to increased anterograde flow, the results of many interventional models in humans suggest that enhancing blood flow in both anterograde and retrograde directions to create a high shear stress oscillatory stimulus may be optimal for improving endothelial function. Well-controlled studies are necessary to further this theory. The purposes of this study were to determine the brachial artery acute shear stress and endothelial function responses to (1) passive heat stress (HEAT), (2) ECG-gated cuff compressions (CUFF), and (3) ECG-gated rhythmic handgrip exercise (HGEX); and (4) to determine if there is a relationship between the degree of shear stress oscillation and endothelial function, regardless of the stimulus applied. We hypothesized that (1) HEAT would increase anterograde shear stress and decrease retrograde shear stress, leading to an unpredictable change in endothelial function; (2) CUFF would increase both anterograde and retrograde shear stress, leading to an increase in endothelial function; (3) HGEX would increase anterograde and retrograde shear stress and exercise metabolites, leading to an increase in endothelial function; and (4) the change in oscillatory shear index would be positively associated with the change in flow-mediated dilation, such that an increment increase in the degree of shear stress oscillation would be accompanied by a proportional improvement in endothelial function. In separate visits, 10 young healthy males (22±3 years) underwent 10 minutes of unilateral HEAT, CUFF, or HGEX on the left arm (EXP), while the right arm served as a within-subject time control (CON). Non-invasive finger plethysmography was used to measure heart rate (HR) and blood pressure (BP) throughout the testing sessions. Ultrasonography was used to obtain measures of blood velocity and arterial diameter from the brachial artery of both limbs throughout the interventions. Anterograde and retrograde shear stress (SS) and oscillatory shear index (OSI) were calculated at baseline and during each intervention to assess the blood flow pattern changes. Endothelial function was assessed before and after each intervention, in both limbs simultaneously using a flow-mediated dilation (FMD) test. HEAT increased HR during the intervention (P < 0.05), mean BP and diastolic BP after the intervention (P < 0.05), anterograde SS in EXP (rest: 15.2 ± 2.9 vs. HEAT: 29.8 ± 8.5 dynes/cm2, P < 0.05), and FMD% in both limbs (P = 0.000). CUFF did not change HR or BP, increased anterograde (rest: 17.9 ± 4.1 vs. CUFF: 43.0 ± 12.4 dynes/cm2, P < 0.05) and retrograde (rest: -3.1 ± 2.5 vs. CUFF: -22.7 ± 6.0 dynes/cm2, P < 0.05) SS in EXP, but did not change FMD% in either limb (P = 0.248). HGEX increased HR during the intervention (P < 0.05), mean BP during and after the intervention (P < 0.05), anterograde SS in EXP (rest: 18.7 ± 5.9 vs. HGEX: 56.4 ± 11.5 dynes/cm2, P < 0.05), and FMD% in both limbs (P = 0.001). These findings suggest that an anterograde-dominant shear stress stimulus may be effective at improving endothelial function, but the confounding effect of sympathetic nervous system activation may play a more dominant role in the acute control response for shorter duration interventions such as the ones explored in this study.