This review elucidates the roles of capillary haemodynamics, nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the remodelling of skeletal muscle microcirculation in response to increased (electrical stimulation) or decreased (chronic ischaemia) blood flow. During early stages of stimulation-induced angiogenesis, up-regulation of VEGF and its receptor VEGF receptor 2 is dependent on shear stress and NO release, whereas later, involvement of NO in the expanding capillary bed appears to be VEGF/VEGF receptor 2 independent. Arteriolar growth most likely relies on mechanical wall stresses while growth factor involvement is less clear. By contrast, in muscles with restricted blood flow, increased VEGF/VEGF receptor 2 expression after ischaemia onset is not associated with changes in shear stress or hypoxia, or capillary growth. After several weeks, VEGF protein levels are lower than normal while modest angiogenesis takes place, a temporal mismatch that limits the utility of using growth factor levels during ischaemia to assess angiogenic potential. Chronic stimulation of ischaemic muscles restores their depressed endothelial-dependent arteriolar dilatation, increases capillary shear stress and VEGF receptor 2 and promotes capillary growth. In patients with peripheral vascular disease, electrical stimulation of ischaemic calf muscles increases blood flow, capillary surface area and muscle performance, offering an alternative ‘endogenous’ treatment to gene or cell therapy.

Keywords:
Muscle activity, Ischaemia, Angiogenesis, Arterioles
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