Localization of Increased Hepatic Vascular Resistance in Liver Cirrhosis

Shibayama, M; Nakata, Katsuji

doi:10.1002/hep.1840050421

Cited by 92 publications

(34 citation statements)

References 17 publications

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“…This is of particular interest in the liver, where local changes in blood flow may be central to major pathologies such as portal hypertension, ascites formation, and hypoxic damage (8). A possible cellular target of ETs within the liver has emerged from recent work on hepatic lipocytes, which are perisinusoidal cells also known as Ito or fat-storing cells.…”

Section: Introductionmentioning

confidence: 99%

Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1.

Housset

Rockey²,

Bissell³

1993

Proc. Natl. Acad. Sci. U.S.A.

293

196

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The endothelins (ETs) form a group of three vasoactive peptides (ET-1, ET-2, and ET-3) for which two types of cellular receptors have been identified, types A and B ET receptors (ETA and ETB receptors, respectively). To address possible targets for ETs within the liver, we isolated the four principal liver cell populations and placed them in short-term primary culture. By ligand-binding assay and mRNA levels, expression of ET receptors was greatest on hepatic lipocytes (Ito cells or fat-storing cells), which are perisinusoidal cells exhibiting features of smooth muscle cells. Moreover, lipocytes expressed both ETA and ETB receptors. The mRNA for ETB receptor, but not for ETA receptor, was detectable in sinusoidal endothelial cells and Kupffer cells; neither mRNA was detectable in hepatocytes. Both ET-1 and ET-3 elicited contraction of activated lipocytes cultured on collagen lattices; the ECSO value for ET-1 was 3 ± 1 nM and for ET-3 was 17 ± 12 nM. In cell isolates from injured liver (after administration of carbon tetrachloride), expression of ET receptors was unchanged. However, mRNA for ET-1 was significantly increased in activated lipocytes, suggesting an autocrine loop for the initiation of lipocyte contraction. The findings imply that ET-1 may play a role in regulating sinusoidal perfusion through its effect on lipocytes, particularly in iDJury states.The endothelins (ETs) are a group of three related peptides (ET-1, ET-2, and ET-3) first described as vasoconstrictors but now known to have an array of metabolic effects (1-3). Specific ET receptors also have been described and are divided into at least two types, termed type A (ETA receptor) (4, 5) and type B (ETB receptor) (6). The ETA receptor is localized largely to vascular smooth muscle and appears to mediate vasoconstrictor effects (7). The ETB receptor is present on a variety of cell types and may subserve other biologic actions of ETs (6, 7).Although studies of ETs have focused on systemic vasoregulation, these peptides may also modulate blood flow locally in specific tissues by autocrine or paracrine routes. This is of particular interest in the liver, where local changes in blood flow may be central to major pathologies such as portal hypertension, ascites formation, and hypoxic damage (8). A possible cellular target of ETs within the liver has emerged from recent work on hepatic lipocytes, which are perisinusoidal cells also known as Ito or fat-storing cells. These cells, particularly in the setting of injury and inflammation, display markers of smooth muscle cells, suggesting contractile potential (9-11).We demonstrate that ET-1 and ET-3 bind to lipocytes via high-affinity receptors and that these peptides are potent agonists of lipocyte contraction. The data have implications for the regulation of hepatic blood flow at the sinusoidal level.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate ...

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Section: Introductionmentioning

confidence: 99%

Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1.

Housset

Rockey²,

Bissell³

1993

Proc. Natl. Acad. Sci. U.S.A.

293

196

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“…Namely, whereas other organs except lungs have a high-pressure circulatory system where blood pressures in the arterioles and venules are 55 and 17 cm H 2 O, respectively, in rats, 10 the liver is preferentially fed by a low-pressure portal venous system where blood pressures in the portal vein at the liver hilum, terminal portal venules, and central (terminal hepatic) venules are 11, 7, and 3 cm H 2 O, respectively, in rats. 11 Corresponding to such low blood pressures, intrahepatic portal veins, in spite of their responsibility for conducting and distributing parenchymal blood flow, are invested with only 1 or 2 layers of smooth muscle cells or are even lacking them in places. 12 Furthermore, hepatic sinusoids consist of fenestrated endothelium and incomplete basement membrane different from capillaries.…”

mentioning

confidence: 99%

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

et al. 2000

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Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution.

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“…Though in early studies the site of the increased resistance was thought to be postsinusoidal, recent works have proved that the presinusoidal resistance is also increased in cirrhotic liver and contributes to the development of portal hypertension [5,6] . In particular, the presinusoidal block is the main cause of the idiopathic portal hypertension and the portal hypertension resulted from chronic biliary obstruction [7,8] .…”

Section: Discussionmentioning

confidence: 99%

A new rat model of portal hypertension induced by intraportal injection of microspheres

Li¹

1998

WJG

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AIM To produce a new rat model of portal hypertension by intraportal injection of microspheres. METHODS Measured aliquots of single or differentsized microspheres (15,40,80µm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial,portal,hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination. RESULTS Portal venous pressure was elevated from basal value of 0.89 -1.02 kPa to a steady-state of 1.98 -3.19 kPa following the sequential injections of single-or different-sized microspheres, with a markedly lowered mean arterial pressure. However, a small-dose injection of 80µm microspheres (1.8×10 5

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Localization of Increased Hepatic Vascular Resistance in Liver Cirrhosis

Cited by 92 publications

References 17 publications

Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1.

Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1.

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

A new rat model of portal hypertension induced by intraportal injection of microspheres

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