Description:
<jats:sec><jats:title>Background</jats:title><jats:p>Signals related to local blood supply lead to an increase of diameter and flow in microvessels upon underperfusion, establishing a negative feedback regulation. Current concepts assume release of metabolic signaling substances in response to low oxygenation from the vessel wall, the tissue or red blood cells. Here, we investigated principles of feedback regulation in the metabolic adaptation of steady state vessel diameters.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A simulation model of vascular diameter adaptation was applied to a mesenteric vascular network (576 segments) to study implications of different assumptions with respect to metabolic signaling on oxygen and blood flow distribution. Deviations of simulated parameters from measured values (velocity, diameter) were analyzed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>1. Oxygen dependence of metabolic signaling is not needed to establish negative feedback regulation due to a ‘dilution effect’ by blood flow. 2. Oxygen dependence does not provide a negative feedback in metabolic signaling by tissue cells in case of insufficient vessel density. 3. Positive feedback and thus instability is evoked, if the amount of metabolic signal producing structures increases with vessel diameter or flow, as is the case in metabolic signaling by RBC.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Surprisingly, oxygen dependence of metabolic signaling is not needed for diameter adaptation under resting conditions in microvascular networks.</jats:p></jats:sec>