Sinusoidal endothelial cell (SEC) porosities were compared between the peri
portal (zone 1) and pericentral (zone 3) regions of the rat liver during re
generation following partial hepatectomy (PHx). SEC porosities and fenestra
tion diameters were measured in control livers, as well as at 5 minutes, 24
, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in bot
h porosity and fenestration diameters were observed in both zones at 5 minu
tes and 5 days following PHx. SEC porosities increased significantly in bot
h zones 1 and 3 within 5 minutes following PHx, but the increase was mainta
ined only in zone 1 at 24 hours after resection. Following the initial rise
, both zones displayed a gradual decrease to less than half their porosity
values at 72 hr post-PHx. After 72 hours, porosities increased to over cont
rol levels and remained elevated until 14 days after PHx. The decrease in p
orosity at 72 hr post-PHx is accompanied by ultrastructural changes within
the sinusoid at this time. Vascular corrosion casting and transmission elec
tron microscopy (TEM) show sinusoid compression resulting from increased he
patic plate widths due to hepatocyte proliferation in the absence of SEC pr
oliferation. Also at this time, we observed many SEC completely enveloped b
y stellate cells. The zonal variations observed for porosities throughout r
egeneration did not correlate with changes in laminin, collagen I and IV, o
r fibronectin deposition within the space of Disse. Taken together, the dat
a reveal that SEC are dynamic regulators of porosity that respond rapidly a
nd locally to environmental zonal stimuli during liver regeneration.