Vascular injury by endotoxin: changes in macromolecular transport parameters in rat aortas in vivo

Vascular injury can lead to enhanced macromolecular transport into the arterial wall. We previously demonstrated that lipopolysaccharide (LPS) -induced injury to rat aorta in vivo caused increases in intimal and medial horseradish peroxidase (HRP) accumulation. In the present study, we quantitatively interpret these LPS-induced changes in HRP transport parameters. The parameters of interest are the permeability (PL) of the luminal blood-tissue boundary (combination of endothelium and internal elastic lamina, IEL), the effective diffusivity (D), and the convective velocity (V) across the media. The parameter values that yield the best fit of the model to the data provide a basis for understanding the tissue changes. The time of peak transmural (medial) accumulation (24 h after LPS injection) correlated with increases in PL (peak, 12-48 h) and preceded the maximum increase in V (peak, 36 h). The monotonic increase in the intimal accumulation during the 5 days after the injury has a time course distinct from the transient increases in PL and from the changes in D, which implies that endothelial permeability has only limited influence on transport beyond the intima. These data implicate the IEL as a barrier to macromolecular transport in the normal aorta and demonstrate that the endothelium and IEL work in concert to determine intimal macromolecular accumulation.