Leg Endothelial Dysfunction Induced by Reduced Daily Physical Activity is Mediated by a Reduction in Shear Stress
Authors: Teixeira André L , Padilla Jaume , Vianna Lauro C. 
Published: November 2023

BackgroundIt is well established that physical inactivity promotes the development of cardiovascular diseases and increases the risk of mortality. Boyle et al. (2013) showed that five days of reduced daily physical activity (i.e. transition from >10,000 to <5,000 steps/day) impaired popliteal artery, but not brachial artery, flow‐mediated dilation (FMD), suggesting that endothelial dysfunction caused by inactivity preferentially manifests in the lower extremities. However, the physiological mechanisms by which physical inactivity causes leg endothelial dysfunction are not fully understood. We hypothesized that a reduction in blood flow‐induced shear stress is a primary underlying mechanism by which reduced daily physical activity impairs popliteal artery FMD.AimTo determine whether preventing the reduction in leg vascular shear stress during five days of reduced physical activity abolishes the detrimental effects of physical inactivity on popliteal artery FMD.MethodsBilateral popliteal artery FMD was measured via high‐resolution Doppler ultrasound (Logiq P5, GE Medical Systems, Milwaukee, WI) at baseline and after five days of reduced daily physical activity in seven healthy and recreationally active male subjects (21 ± 3 years; 179 ± 4 cm, 80 ± 8 kg; mean ± SD). Subjects were instructed to reduce daily physical activity by a transition from high (>10,000 steps/day) to low daily physical activity (<5,000 steps/day) and refraining from planned exercise. Steps per day were measured by accelerometers (Garmin, vívofit, Brazil). During the five days of reduced daily physical activity, one foot was submerged in 40–42°C water (i.e., heated leg), three times a day for 30‐min each period, to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated leg).ResultsThe number of steps significantly decreased in the reduced daily physical activity phase compared with baseline (baseline vs. reduced daily physical activity phase: 13764 ± 840 steps/day vs. 3835 ± 219 steps/day, mean ± SE, P < 0.01). During the heating protocol, popliteal artery mean shear rate significantly increased in the heated leg (Δ111.4 ± 44.3%, P < 0.01) but not in the nonheated leg (Δ −17.1 ± 9.4%, P = 0.22). Popliteal artery FMD was impaired after five days of reduced daily physical activity in the nonheated leg (pre: 6.8 ± 0.60 % vs. post: 3.2 ± 0.53 %, P = 0.03), but was unchanged in the heated leg (pre: 6.8 ± 0.39 % vs. post: 6.5 ± 0.54 %, P = 0.97). In addition, baseline diameter was not impacted by five days of reduced daily physical activity in any heated (pre: 5.69 ± 0.28 mm vs. post: 5.56 ± 0.26 mm, P = 0.15) or nonheated leg (pre: 5.86 ± 0.26 mm vs. post: 5.76 ± 0.30 mm, P = 0.20).ConclusionThese results support the hypothesis that reduced leg blood flow‐induced shear stress during physical inactivity is a key underlying mechanism mediating leg endothelial dysfunction associated with inactivity.Support or Funding InformationCAPES, CNPq and FAPDF.