ET-1 induced alterations of hepatic microcirculation: sinusoidal and extrasinusoidal sites of action
Bauer, M.; Zhang, J.X.; Bauer, I.; Clemens, M.G.
American Journal of Physiology 267(1 Pt 1): G143-G149
1994
ISSN/ISBN: 0002-9513 PMID: 8048527 Document Number: 427180
Using epifluorescence microscopy, we investigated the dynamic changes in hepatic sinusoidal hemodynamics in vivo during continuous infusion of endothelin- 1 (ET- 1) in pentobarbital-anesthetized rats. ET-1 was infused for 20 min at rates of 2 or 10 pmol/min either systemically or into the portal vein, followed by a 90-min recovery period. In contrast to systemic application of ET-1 that did not cause a consistent hepatic microvascular effect, we observed two different patterns of microcirculatory alterations during portal application. Infusion of 2 pmol/min elicited a rapid, reversible decrease in sinusoidal diameter that was paralleled by a slight increase in red cell velocity, resulting in conservation of volumetric flow and sinusoid density. Infusion of 10 pmol/min resulted in a biphasic narrowing followed by transient increase in sinusoidal diameter and a profound and lasting decrease in red cell velocity, leading to an almost complete cessation of hepatic microvascular blood flow. These results indicate that ET-1 is a potent constrictor in the liver microcirculation in vivo and acts at both extrasinusoidal and sinusoidal sites, although the sinusoidal sites appear to be more sensitive to lower concentrations.