Distinct structural and functional angiogenic responses are induced by different mechanical stimuli

Adequacy of the microcirculation is essential for maintaining repetitive skeletal muscle function while avoiding fatigue. It is unclear, however, whether capillary remodelling after different angiogenic stimuli is comparable in terms of vessel distribution and consequent functional adaptations. We determined the physiological consequences of two distinct mechanotransductive stimuli: (1) overload-mediated abluminal stretch (OV); (2) vasodilator-induced shear stress (prazosin, PR).

In situ EDL fatigue resistance was determined after 7 or 14 days of intervention, in addition to measurements of femoral artery flow. Microvascular composition (muscle histology) and oxidative capacity (citrate synthase activity) were quantified, and muscle PO₂ calculated using advanced mathematical modelling.

Compared to controls, capillary-to-fiber ratio was higher after OV14 (134%, p < .001) and PR14 (121%, p < .05), although fatigue resistance only improved after overload (7 days: 135%, 14 days: 125%, p < .05). In addition, muscle overload improved local capillary supply indices and reduced CS activity, while prazosin treatment failed to alter either index of aerobic capacity.

Targeted capillary growth in response to abluminal stretch is a potent driver of improved muscle fatigue resistance, while shear stress-driven angiogenesis has no beneficial effect on muscle function. In terms of capillarity, more is not necessarily better.