Hepatic artery and portal vein remodeling in rat liver: Vascular response to selective cholangiocyte proliferation

Three-dimensional reconstruction of the biliary tree, hepatic artery, and portal vein in normal rats and rats fed α-naphthylisothiocyanate (ANIT), a compound that causes selective proliferation of epithelial cells (ie, cholangiocytes) that line the bile ducts, was performed. All hepatic structures in ANIT-fed rats branched 1.5 times more often than in normal rats, reflecting an increased number of segments, whereas the length of the biliary tree, hepatic artery, and portal vein remain unchanged. The length of the proximal vessel segments was uniform in both groups of rats whereas the length of distal segments decreased twofold in ANIT-fed rats, suggesting that small vessels preferentially undergo proliferation. In contrast, the length of all bile duct segments decreased twofold, suggesting that ANIT induced proliferation of all compartments of the biliary tree. The total volume of the biliary tree, hepatic artery, and portal vein was increased 18, 4, and 3 times, respectively, after ANIT feeding. The diameters of the bile ducts (range, 20 to 259 μm) and arterial (range, 21 to 276 μm) segments in ANIT-fed rats did not differ from normal rats (range, 21 to 245 μm and 20 to 265 μm, respectively). In contrast, the diameters of proximal venous segments in ANIT-fed rats were significantly less (316 ± 68 μm versus 488 ± 89 μm, P<0.001). The data suggest that after experimentally induced cholangiocyte proliferation, the hepatic artery and portal vein also undergo marked proliferation, presumably to support the increased nutritional and functional demands of the proliferated bile ducts. The molecular mechanisms of these vascular changes remain to be determined.