title: 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.
abstract: 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.
authors.affiliation: Department of Anatomy, Osaka City University Medical School, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kaneda
authors.forename: W
authors.initials: W
authors.lastname: Ekataksin
authors.forename: M
authors.initials: M
authors.lastname: Sogawa
authors.forename: A
authors.initials: A
authors.lastname: Matsumura
authors.forename: A
authors.initials: A
authors.lastname: Cho
authors.forename: N
authors.initials: N
authors.lastname: Kawada
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000648:ultrastructure; D006975:Hypertension, Portal / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D017082:Portal Pressure / Q000187:drug effects*; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D019332:Endothelin-1