There are two possible routes for passive, non-specific transfer across the microvascular endothelial layer, through the cells or around them. The paracellular pathway is “blocked” by the presence of tight junctions but this pathway may still be the principal route for the passive fluxes of small solutes that are barred from the transcellular route by being too polar (mannitol, sucrose and inulin are considered in Appendix B). In addition to neutral molecules like mannitol, the paracellular pathway may be measurably permeable to Na+ and Cl− [151]. As discussed in detail in [4] and in Sect. 5.6 evidence for this includes the observation that the tracer fluxes of Na+ and Cl− are not affected by ouabain [152] or bumetanide [153], agents that specifically inhibit ion transporters known to be involved in transcellular fluxes of these ions.