Hepatic response to right ventricular pressure overload.
OBJECTIVE
Modifying the afferent blood supply to the liver does not change the zonal expression pattern of hepatic enzymes in the rat.


METHODS
We used pulmonary trunk banding (PTB) to study the effect of an efferent hindrance of blood flow on hepatic architecture and zonation of gene expression.


RESULTS
Most PTB rats developed right ventricular hypertrophy and congestive heart failure. The hepatic response to PTB developed concomitantly with the decline in heart function. Enzyme expression in the periportal region was not affected, but the pericentral rim of hepatocytes expressing glutamine synthetase, ornithine aminotransferase, and NADPH cytochrome P-450 reductase (CYPred) first declined in diameter, then became discontinuous, and finally disappeared. Meanwhile, ornithine aminotransferase and especially CYPred, became re-expressed in the periportal zone. These changes occurred without appreciable cell death or fibrotic changes; the expression of fibronectin and alpha-smooth muscle actin increased perisinusoidally, but that of collagen did not. Electron microscopic analysis revealed normal fenestration of the sinusoidal endothelial cells without detectable deposition of basement membrane material, but both the width of the space of Disse and the length and number of hepatic microvilli were significantly reduced, implying a decreased flow of fluid in the space of Disse.


CONCLUSIONS
The reprogramming of gene expression in livers with a postsinusoidal hindrance of blood flow results from declining access of the hepatocytes to intrasinusoidal signal-transduction molecules and suggest that the impaired biotransformation that accompanies right ventricular failure is caused by a central-to-portal shift in expression of the corresponding enzymes.
AMC Liver Center, Academic Medical Center, University of Amsterdam, The Netherlands.
Roben G
RG
Gieling
Jan M
JM
Ruijter
Adri A W
AA
Maas
Marius A
MA
Van Den Bergh Weerman
Koert P
KP
Dingemans
Fibo J W
FJ
ten Kate
Ronald H
RH
Lekanne dit Deprez
Antoon F M
AF
Moorman
Wouter H
WH
Lamers
D000818:Animals; D002496:Central Venous Pressure; D003094:Collagen / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D020869:Gene Expression Profiling; D005974:Glutamate-Ammonia Ligase / Q000032:analysis; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009953:Ornithine-Oxo-Acid Transaminase / Q000032:analysis; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D003094:Collagen; D009953:Ornithine-Oxo-Acid Transaminase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005974:Glutamate-Ammonia Ligase