Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors?

Reglin B, Secomb TW, Pries AR. Structural adaptation of microvessel diameters in response to metabolic stimuli: where are the oxygen sensors? Am J Physiol Heart Circ Physiol 297: H2206-H2219, 2009. First published September 25, 2009; doi:10.1152/ajpheart.00348.2009. Maintenance of functional vascular networks requires structural adaptation of vessel diameters in response to hemodynamic and metabolic conditions. The mechanisms by which diameters respond to the metabolic state are not known, but may involve the release of vasoactive substances in response to low oxygen by tissue (tissue signaling, e. g., CO2, adenosine), by vessel walls (wall signaling, e. g., prostaglandins, adenosine), and/or by red blood cells (RBCs) (RBC signaling, e. g., ATP and nitric oxide). Here, the goal was to test the potential of each of these locations of oxygen-dependent signaling to control steady-state vascular diameters and tissue oxygenation. A previously developed theoretical model of structural diameter adaptation based on experimental data on microvascular network morphology and hemodynamics was used. Resulting network characteristics were analyzed with regard to tissue oxygenation (Oxdef; percentage of tissue volume with PO2 < 1 Torr) and the difference between estimated blood flow velocities and corresponding experimental data [velocity error (V-err); root mean square deviation of estimated vs. measured velocity]. Wall signaling led to Oxdef < 1% and to the closest hemodynamic similarity (V-err: 0.60). Tissue signaling also resulted in a low oxygen deficit, but a higher V-err (0.73) and systematic diameter deviations. RBC signaling led to widespread hypoxia (Oxdef: 4.7%), unrealistic velocity distributions (V-err: 0.81), and shrinkage of small vessels. The results suggest that wall signaling plays a central role in structural control of vessel diameters in microvascular networks of given angioarchitecture. Tissue-derived and RBC-derived signaling of oxygen levels may be more relevant for the regulation of angiogenesis and/or smooth muscle tone.