Differential Expansion of the Capillary Bed through Physiological Angiogenesis in Skeletal Muscle

Abstract

A range of well‐established in vivo models of angiogenesis currently exists, involving surgical and pharmacological intervention. These approaches generally improve global measures of microvascular supply, but are rarely interrogated for their capacity to improve tissue oxygen tension. The aim of this research was to characterise a variety of muscle recruitment patterns known to induce angiogenesis, determine their effect on capillary spatial heterogeneity, and subsequently local tissue oxygen delivery.Male Wistar rats underwent seven days of angiogenic remodelling through indirect electrical stimulation of skeletal muscle (at 4, 10 or 40Hz), muscular overload (through synergist ablation) or pharmacological supplementation (Prazosin, alpha‐adrenergic blocker). Muscle samples were snap frozen and capillary content identified through Griffonia simplicifolia lectin staining, with morphometric analysis of muscle composition used as the basis for oxygen consumption modelling.We demonstrated that seven days of supramaximal indirect electrical stimulation induced significant angiogenesis (capillary to fibre ratio (C:F) increased by 59, 36 and 45% for 4, 10 and 40Hz, respectively). A similar response for muscular overload and prazosin supplementation were seen with a 42 and 27% increase, respectively. This improvement in capillarity was accompanied by a reduction in mean capillary domain size (tissue supply area), but with varying degrees of spatial heterogeneity.Skeletal muscle overload and 40Hz electrical stimulation showed a substantially more homogeneous capillary distribution, and subsequently improved tissue oxygenation at high levels of simulated exercise. Conversely, the improved capillarity associated with prazosin and 4Hz electrical stimulation showed no extensive change in capillary distribution. We therefore conclude that mechanical stimulation of angiogenesis may be accentuated by a metabolic component.