Introduction: Metabolic stimuli are necessary to generate and maintain functionally adequate microvascular networks. Low oxygen content has been shown to evoke the release of vasoactive substances by the tissue (e.g. adenosine), by RBC (ATP, NO) and by the vessel wall (e.g. adenosine). Here, we investigate origin and release characteristics of metabolic signals.

Methods: In the model used, all vessels of a rat mesentery microvascular network change their diameter in response to wall shear stress, transmural pressure and the assumed metabolic signal. Network structures resulting from angioadaptation, assuming metabolic signal production by the tissue, RBC or vessel wall, respectively, were analysed with respect to (A) functional adequacy (low oxygen deficit, OxDef, of the tissue) and (B) similarity to in vivo observations (low deviation between predicted and measured flow velocities, Verr). Signals were generated in dependence on local oxygen (Ox) or at a constant rate (Const).

Results:

Wall Tissue RBC

Ox Const Ox Const Ox Const

OxDef, % 0 0 0 0 16 28

Verr 0.61 0.67 0.74 0.72 0.96 1.13

Conclusion: Although various mechanisms prevent tissue oxygen deficit, signalling by the vessel wall seems to be best suited to generate functionally adequate and realistic network structures.