Adaptation of microvascular networks to local oxygenation: Functional roles of tissue, vessel wall and RBC signalling

Metabolic mechanisms play an important role in the control of microvascular diameters and perfusion. Recently we have reported that for structural diameter adaptation in steady state, signals originating in the vessel wall in response to local Po2 may be central. However, extensive literature shows that oxygen dependent signals from the tissue or RBC are also capable of affecting vessel diameter. Therefore, we address characteristics of tissue, vessel wall and RBC signalling in vascular control and the possible interaction of these mechanisms in structural diameter adaptation. A previously developed simulation model of structural diameter adaptation in microvascular networks was used. Adaptation was simulated for a mesenterial network (576 segments) and an artificial test network (4 segments) with varying geometry. For the mesenteric network, all combinations of oxygen sensing mechanisms resulted in less realistic network hemodynamics than solitary action of wall signalling stressing its role in structural diameter adaptation. For structural diameter adaptation RBC signalling is less well suited because of phase separation effects limiting signalling strength. In case of insufficient vessel density, only tissue signalling can properly induce angiogenesis. In summary, individual modes of metabolic sensing are differently suited for individual components of vascular adaptation.