ET-1 induced alterations of hepatic microcirculation: sinusoidal and extrasinusoidal sites of action.
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.
Bauer
M
M
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
Zhang
J X
JX
Bauer
I
I
Clemens
M G
MG
D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D011168:Portal System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
D016232:Endothelins