Hemodynamic and Microvascular Adaptations to Aerobic Training Intensity Improve Maximal Oxygen Consumption

Abstract Background Aerobic training enhances VO₂ max , yet the contribution of peripheral microvascular remodeling to this improvement remains insufficiently understood. This research demonstrates how two distinct training modalities, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), influence oxygen transport dynamics and microvascular remodeling. Methods Twenty-five healthy sedentary adults (15 women, 10 men; mean age 25 ± 2 years; normal BMI) were randomly assigned to HIIT or MICT for 8 weeks. VO₂ max was assessed before and after the training program. 15 participants underwent non-invasive maximal cardiac output measurement (Q max ), while vastus lateralis muscle biopsies were obtained from 10 participants. Tissue samples were cleared and immunolabeled for VE-cadherin and alpha-smooth muscle actin to observe microvasculature architecture. A computational hemodynamic model integrating cardiac output and microvascular parameters was constructed to estimate flow dynamics. Results VO₂ max increased significantly in both training groups, with a greater improvement in HIIT (p = 0.024). Q max increased similarly in both groups (p = 0.001), while calculated arteriovenous oxygen difference (a-vO₂ diff) showed a trend toward improvement only in HIIT. No formation of new capillaries nor anastomoses (angiogenesis) was detected in either group; however, both HIIT and MICT induced significant capillary and venule dilation. Notably, only HIIT led to a significant increase in pericyte coverage (p = 0.047). Venules of both groups exhibited dilation accompanied by increased surrounding smooth muscle cells. No remodeling was found in arterioles. Hemodynamic modelisation estimated higher shear stress during HIIT than MICT and vasodilation tended to decrease shear stress over time during both training. Furthermore, pericyte recruitment was modelized to adapt to shear stress level limiting excessive capillary dilation during high effort intensity. Conclusion HIIT induces superior improvements in VO₂ max and distinct microvascular structural adaptations rather than angiogenesis. HIIT is supposed to stimulate a protective adaptation at the capillary level, limiting excessive dilation during maximal effort. Our hemodynamic model supports this shear stress-dependent mechanism. These findings underscore the role of exercise intensity and hemodynamics in shaping microvascular responses to endurance training. Clinical Perspective Peripheral adaptation to exercise is linked with the dilation of muscle capillaries and venules. Mechanoadaptive responses, rather than growth factor-mediated angiogenesis, drive the remodeling of the muscle microvasculature. High-intensity interval training elicits higher shear stress than moderate continuous interval training, linking the adaptation of the microvasculature to increased blood flow as the primary factor that explains the superiority of HIIT compared to MICT in improving maximal oxygen consumption. Clinical implication Training regimens should focus on increasing peripheral flow and shear stress to initiate microvasculature remodeling. Potentiating mechanoadaptative responses and microcirculation remodeling would provide a means to improve cardiovascular function and fitness