Endothelin-1-induced vasoconstriction causes a significant increase in portal pressure of rat liver: localized constrictive effect on the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstruction

Hepatology. 1998 Mar;27(3):735-47. doi: 10.1002/hep.510270315.


Intraportal infusion of endothelin-1 (ET-1), a potent vasoconstrictor, significantly elevates portal venous pressure. To determine the major site of vascular constriction in the intrahepatic porto-sinusoidal system, we performed an in situ perfusion of rat livers with 1 nmol/L ET-1 at a flow rate of 20 mL/min. Portal pressure rose from 22 cm H2O to 54 cm H2O within 25 minutes. Specimens were prepared for light-microscopic serial reconstruction and electron microscopy. The distal segment of preterminal portal venules (DS/PPV) with an inner diameter of 40 to 80 microm showed complete obliteration of the lumen over a 300-microm distance caused by the intense contraction of perivascular smooth muscle cells and protruding of endothelial cells into the lumen. The proximal segment of preterminal portal venules (PS/PPV) with a larger diameter up to 150 microm also underwent strong constriction, but still had luminal space for the flow, while the PS/PPV with a diameter of 150 to 400 microm showed moderate or mild constriction and retained a wide lumen. Neither terminal portal venules, inlet venules, sinusoids, nor central veins, however, exhibited demonstrable constriction. Liver parenchyma fed by the inlet venules that emerged from the PS/PPV exhibited a wide sinusoidal lumen and vacuolated hepatocytes caused by the influx of excess portal perfusate that escaped from the occlusive areas. The present study has revealed that the DS/PPV functions as a presinusoidal quasi-sphincter mechanism and is involved in the redistribution of intrahepatic portal flow under increased portal pressure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelin-1 / pharmacology*
  • Endothelium, Vascular / ultrastructure
  • Hypertension, Portal / pathology
  • Male
  • Microscopy, Electron
  • Portal Pressure / drug effects*
  • Portal Vein / cytology
  • Portal Vein / drug effects*
  • Portal Vein / ultrastructure
  • Rats
  • Rats, Wistar
  • Vasoconstriction / drug effects*


  • Endothelin-1