The Role of Group III/IV Muscle Afferents in Regulating the Hemodynamic Response to Whole Body Exercise

BACKGROUND Group III/IV muscle afferents respond to mechanical and chemical stimuli occurring in skeletal muscle during exercise and contribute, via their feedback to cardiovascular control centers in the brainstem, to the circulatory response to physical activity. In healthy young individuals, feedback from these afferents facilitates leg blood flow during dynamic knee extensor exercise. However, their exact role in determining peripheral hemodynamics during whole body exercise (large active muscle mass), which is characterized by larger sympathetically‐mediated vasoconstriction compared to knee extensor exercise (small active muscle mass), has yet to be investigated. METHODS Separated by 2 h of rest, 4 healthy males (Age 21 ± 2 yrs) completed 3 bouts of cycling exercise [75 W: ~45% of VO 2 max, 100 W: ~55% VO 2 max, and 80% of peak power output (226 ± 12 W): ~95% VO 2 max] under both control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) blocking μ‐opioid receptor‐sensitive muscle afferents. To avoid different respiratory muscle metaboreflex and/or chemoreflex effects on leg vascular conductance (LVC) and blood flow, subjects’ breathing during FENT (usually characterized by hypoventilation and asphyxia) was guided to achieve end‐tidal PCO 2 (P ET CO 2 ) to be similar to that in CTRL. Femoral arterial blood flow (Q L ; Doppler Ultrasound), heart rate (HR), cardiac output (CO), and leg perfusion pressure (PP; intravascular catheter, arterial – venous blood pressure) were continuously determined, femoral arterial and venous blood samples were collected during the final minute of each workload. RESULTS There were no hemodynamic differences between conditions at rest. Arterial blood gases, breathing, and P ET CO 2 were, per design, not different between conditions. During FENT exercise, PP was, compared to CTRL, significantly lower at all intensities (up to 26%). Without affecting HR (P > 0.2), CO was significantly lower during FENT compared to CTRL at 75 W and 100 W (up to 25%), but not at 80% W peak . Q L was, however, not different between conditions (P = 0.69) as leg vascular conductance was up to 33% higher during FENT compared to CTRL (P < 0.05). Arterial O 2 content, leg O 2 delivery, and leg VO 2 were similar between conditions (P > 0.3). CONCLUSION The current findings obtained from humans during leg cycling suggest that group III/IV‐mediated afferent feedback from locomotor muscle facilitates leg perfusion pressure and CO, but restricts leg vascular conductance during whole body exercise. These effects of group III/IV muscle afferents are likely secondary to their role in regulating the autonomic control of the heart and the vasculature. Interestingly, the effect of these sensory neurons on leg vascular conductance differs between exercise characterized by large vs small active muscle mass. While afferent blockade increases leg vascular conductance (with no changes in Q L , but decreases in PP) during cycling exercise, it decreases leg vascular conductance (relatively larger fall in Q L compared to fall in PP) during knee extensor exercise. Support or Funding Information National Heart, Lung, and Blood Institute (HL‐116579)