On the adaptive significance of group III/IV muscle afferent feedback for the cardiovascular response during sustained locomotion in humans

While the cardiovascular consequences of group III/IV muscle afferent feedback have been studied during short‐duration exercise, its role during sustained (> 5 min) locomotion remains unknown. Thirteen healthy individuals (4f/9m) completed two 20‐min cycling bouts at ∼50% (moderate) and ∼75% (heavy) of with intact (CTRL) and pharmacologically attenuated (FENT; lumbar intrathecal fentanyl) group III/IV leg muscle afferent feedback. Cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF) and leg vascular conductance (LVC) were quantified. While cardiovascular responses at rest were not different between conditions, afferent blockade reduced CO during the moderate‐intensity exercise ( P = 0.006), with the impact progressively strengthening over time ( P = 0.027). These effects were absent during the heavy‐intensity bout ( P = 0.741). For moderate‐intensity exercise, MAP was consistently ∼10% lower ( P < 0.001) and LVC ∼13% higher ( P = 0.006) during FENT compared to CTRL. During heavy‐intensity exercise, MAP was steadily ∼14% lower during FENT ( P < 0.001) and LVC was higher ( P < 0.001) with progressive increases over time ( P = 0.019). Afferent blockade had no effect on LBF throughout the moderate‐intensity exercise ( P = 0.407). However, during heavy‐intensity exercise, starting from minute 10, there was a between‐condition difference, resulting in a significantly higher LBF (∼9%) during FENT compared to CTRL ( P = 0.010). These findings highlight the importance of group III/IV leg muscle afferent feedback for regulating the cardiovascular response to human locomotion but also indicate that its relative contribution varies with the intensity and duration of the exercise. image Key points While the cardiovascular significance of group III/IV muscle afferent feedback has been investigated during short‐duration exercise (≤5 min), its functional relevance during prolonged locomotion is unknown. Using lumbar intrathecal fentanyl to attenuate leg muscle afferent feedback during 20‐min cycling bouts at ∼50% and ∼75% , we found that these afferents consistently facilitate blood pressure, with effects amplifying with intensity. They also progressively restrict leg vascular conductance, particularly during heavy‐intensity exercise, creating a cumulative constraint on blood flow that emerges over time rather than immediately. We also found that group III/IV muscle‐afferents augment cardiac output during moderate‐intensity exercise, with this effect strengthening over time. However, this facilitation disappears completely during heavy‐intensity exercise. These findings demonstrate that muscle afferent feedback dynamically modulates haemodynamic responses during sustained locomotion, with cardiovascular contributions varying substantially based on both exercise intensity and duration, a complexity not apparent in short‐duration protocols.