Why Does Angiogenesis Not Reduce Acidosis and Hypoxia?
When the tumor as a whole is considered, an increase in vascular density should decrease resistance and increase blood flow, but this does not occur. This apparent contradiction likely arises from the evolution of regional heterogeneity during tumor growth and development. Pries and colleagues (140) have recently developed a model to describe how each segment of a microvascular network adjusts structurally in response to local stimuli and have compared these results with normal tissue (rat mesentery). They demonstrated that a minimal set of four types of adaptive responses is required to produce stable and realistic network structures (Table 1). The shear-dependent response causes enlargement of vessels carrying relatively large flow rates. The pressure-dependent response is responsible for the asymmetry of the vascular system, with arterioles smaller than corresponding venules. Responsiveness of local metabolic conditions, and the conduction of this information along upstream and down
