Intravital and Electron Microscopic Observation of Ito Cells in Rat Hepatic Microcirculation

Suematsu, Makoto; Oda, Masaya; Suzuki, Hidekazu; Kaneko, Hiroshi; Watanabe, Norihito; Furusho, Tadasu; Masushige, Shoichi; Tsuchiya, Masaharu

doi:10.1006/mvre.1993.1033

Cited by 53 publications

(36 citation statements)

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“…An analog of bosentan devoid of binding affinity for endolate flow much as pericytes regulate blood flow through thelin receptors and without pharmacological activity had no effect on portal systemic capillaries. 6,8,10,[30][31][32][33] In this study we show that he-pressure in cirrhotic livers (not shown). Bosentan had no effect on portal prespatic injury and particularly cirrhosis (induced by CCl 4 ) are sure in normal animals (not shown).…”

Section: Effect Of the Endothelin Antagonist Bosentan On Portalmentioning

confidence: 65%

Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance

Rockey¹

1996

Hepatology

134

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by two major endothelin receptors, endothelin A (ET A ) and Hepatic stellate cells are similar to tissue pericytes endothelin B (ET B ). 2-3 ET A receptors are abundant on vascuand have been shown to be contractile. In this study, we lar smooth muscle cells, have a high affinity for endothelinexamined the effects of known mediators of stellate cell 1, produce sustained contraction of vascular smooth muscle contraction on portal pressure in rat livers after carbon cells, and mediate vasoconstriction. 3 In contrast, ET B receptetrachloride induced injury (including cirrhosis) and tors bind both endothelin-1 and endothelin-3 with equal affininvestigated the contractility of stellate cells as a funcity. The ET B receptor appears to mediate either vasoconstriction of liver injury. Sarafotoxin S6C, an endothelin B tion or vasorelaxation depending on tissue type. 4 As such, (ET B ) receptor agonist, had minor effects on portal presthe endothelins are implicated in normal physiological as sure when perfused into normal livers at concentrations well as pathological responses. known to elicit stellate cell contraction (2 nmol/L). In Early work in liver has shown that endothelin-1 and endocontrast, both endothelin-1 (2 nmol/L) and angiotensin thelin-3 perfused into the portal system results in elevation II (8.6 nmol/L) caused a rapid and pronounced rise in of portal pressure and an increase in glycogenolysis. [5][6][7] Addiportal pressure. The effects of sarafotoxin S6C (a potent tionally, endothelin-1 may mediate sinusoidal vasoconstricstellate cell contractile agonist) on portal pressure were tion induced by ethanol. 8 While the precise mechanism by greater in cirrhotic than normal liver, whereas those of which endothelin-1 and endothelin-3 cause vasoconstriction angiotensin II were unchanged after liver injury. Endoin liver is unknown, it has been proposed that they act on thelin-1 and sarafotoxin S6C The tent with its inhibitory effect on stellate cell contraction.most compelling evidence that endothelin may mediate sinuWe conclude that stellate cell contractility increases soidal vasoconstriction via its effects on stellate cells stems with progressive liver injury and is proportional to the from work directly showing their contraction in response to degree of stellate cell activation, becoming most promiendothelin-1 and endothelin-3. 13-15 nent in the cirrhotic liver. Endothelin-stimulated conDuring liver injury, stellate cells undergo a process charactraction of stellate cells in cirrhotic liver may contribute terized by loss of retinoid droplets, enhanced collagen producto increased intrahepatic resistance and portal prestion, and expression of smooth muscle a actin, which has sure. (HEPATOLOGY 1996;24:233-240.) been termed ''activation''. 16 It occurs spontaneously in cultured stellate cells, and in vivo during liver injury. 17 Further The three known endothelins comprise a family of homolo-studies have indirectly suggested that myofibroblasts (i.e., gous 21 amino acid peptides. 1,2 While they have diverse ef-acti...

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Section: Effect Of the Endothelin Antagonist Bosentan On Portalmentioning

confidence: 65%

Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance

Rockey¹

1996

Hepatology

134

View full text Add to dashboard Cite

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“…Means Ϯ SEM, *P Ͻ .05 vs. control. 11 and completely eliminated vitamin A autofluorescence within Ϸ20 seconds of exposure because of its rapid photobleaching property. 11 Emission maxima of collagen above 435 nm 12,13 allowed for detection of these extracellular matrix composites by switching to blue and green fluorescence epi-illumination (filter sets [02] and [15]), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…11 and completely eliminated vitamin A autofluorescence within Ϸ20 seconds of exposure because of its rapid photobleaching property. 11 Emission maxima of collagen above 435 nm 12,13 allowed for detection of these extracellular matrix composites by switching to blue and green fluorescence epi-illumination (filter sets [02] and [15]), respectively. Subsequently, contrast enhancement for visualization of the hepatic microvasculature was achieved by intravenous injection of 5% fluorescein isothiocyanate (FITC)-labeled dextran (molecular weight, 150,000; 0.1 mL/100 g body weight; Sigma, Deisenhofen, Germany) and epi-illumination with blue light (450-490 nm/Ͼ520 nm).…”

Section: Methodsmentioning

confidence: 99%

“…23 Using ultraviolet epi-illumination, Ito cells are easily identified in vivo by the autofluorescence of intracellularly stored vitamin A. 11,14 First applying this technique in CCl 4 -exposed rats, we were able to monitor on-line the change of spatial distribution of Ito cells with accumulation in fibrous septa. The simultaneous quantitative assessment of autofluorescent collageneous structures by switching the filter set and, thus, excitation and emission wavelengths enabled the direct temporal and spatial correlation between the key events in liver fibrogenesis, i.e., Ito cell activation and extracellular matrix deposition in vivo.…”

Section: Grossmentioning

confidence: 99%

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An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats

1998

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Quantitative data defining the relationship between the hepatic microcirculation and the development of liver pathological changes could provide a basis for a better understanding of fibrogenic processes, such as cirrhosis. Therefore, we established the technique of intravital fluorescence microscopy and computer-assisted microcirculation analysis systems in developing cirrhosis in rats with the aim of quantitatively assessing the association of hepatic microvascular morphology with its disordered acinar architecture, and nonparenchymal cell transformation with collagen deposition, parenchymal cell loss, and liver dysfunction. In animals chronically exposed to carbon tetrachloride The pathological process of developing cirrhosis represents an almost inconceivably complex network of interacting cells, fibrogenic mediators, and extracellular matrix molecules (ECM). 1 Dramatic improvements in cell and molecular biological techniques now permit a detailed analysis of the composition, structure, immunology, and histological localization of the individual components of extracellular matrix. Dissection of the cellular and molecular pathobiology of ECM deposition includes the identification of the cellular sources of specific ECM components as well as the definition of humoral factors and regulatory loops underlying both the amplification and degradation pathways of ECM molecules during fibrogenesis. 2 Beside these molecular aspects of fibrogenesis, vascular modifications during the development of cirrhosis have fully been recognized and interpreted in that microvascular changes in the liver are not the mere consequence of fibrosis and nodule formation, but dominate the entire development of the pathological condition. 3 Microvascular corrosion casts observed by scanning electron microscopy have proved useful in demonstrating microvascular morphology in hepatic cirrhosis [4][5][6][7][8] ; however, these techniques are neither suited for the investigation of dynamic alterations in the microvascular function nor for the direct assessment of the close interrelation between the hepatic microcirculation and liver structure and function. Combining several applications of intravital fluorescence microscopy in a rat model of developing cirrhosis, the present study provides the first in vivo appreciation of the association of microvascular, cellular, and functional aspects during the process of hepatic organ remodeling. MATERIALS AND METHODSAnimal Model.

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“…25,26 Whether the contractile properties of these cells actually underlie sinusoidal narrowing has not fully been documented as yet in vivo. However, microfluorography of perfused liver ex vivo 21,24,27 or high-resolution analysis by intravital microscopy 28,29 support the concept.…”

Section: Distribution Of Ho and Microtopographic Basis For Co-mediatementioning

confidence: 99%

The heme oxygenase-carbon monoxide system: u regulator of hepatobiliary function

2000

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Intravital and Electron Microscopic Observation of Ito Cells in Rat Hepatic Microcirculation

Cited by 53 publications

References 0 publications

Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance

Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance

An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats

The heme oxygenase-carbon monoxide system: u regulator of hepatobiliary function

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