α1-Adrenergic effects and liver regeneration

Cruise, Jennifer L.; Knechtle, Stuart J.; Bollinger, R. Randal; Kuhn, Cynthia M.; Michalopoulos, George K.

doi:10.1002/hep.1840070604

Cited by 189 publications

(116 citation statements)

References 27 publications

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“…18,19 Additionally, at the point of initiation of SEC proliferation around 72 hours after PHx, cell-cell interactions may play a pivotal role in influencing the reduction of fenestrations via soluble agents. Likewise, undisclosed soluble molecules, including proteases, growth factors, and adrenergics, that rise in the blood immediately following PHx may also influence dilation of fenestrations during the first 24 hours following resection, 1,2,43,44,48 as well as their subsequent decrease thereafter. We have undertaken a quantitative ultrastructural study that clearly has limitations in identifying such agents, but our results indicate the critical importance of evaluting these agents in the context of fenestration diameter regulation in future studies.…”

Section: Ultrastructural Examination Of Sinusoids During Regenerationmentioning

confidence: 99%

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver

et al. 2001

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Sinusoidal endothelial cell (SEC) porosities were compared between the periportal (zone 1) and pericentral (zone 3) regions of the rat liver during regeneration following partial hepatectomy (PHx). SEC porosities and fenestration diameters were measured in control livers, as well as at 5 minutes, 24, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in both porosity and fenestration diameters were observed in both zones at 5 minutes and 5 days following PHx. SEC porosities increased significantly in both zones 1 and 3 within 5 minutes following PHx, but the increase was maintained only in zone 1 at 24 hours after resection. Following the initial rise, both zones displayed a gradual decrease to less than half their porosity values at 72 hr post-PHx. After 72 hours, porosities increased to over control levels and remained elevated until 14 days after PHx. The decrease in porosity at 72 hr post-PHx is accompanied by ultrastructural changes within the sinusoid at this time. Vascular corrosion casting and transmission electron microscopy (TEM) show sinusoid compression resulting from increased hepatic plate widths due to hepatocyte proliferation in the absence of SEC proliferation. Also at this time, we observed many SEC completely enveloped by stellate cells. The zonal variations observed for porosities throughout regeneration did not correlate with changes in laminin, collagen I and IV, or fibronectin deposition within the space of Disse. Taken together, the data reveal that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration. (HEPATOLOGY 2001;33:363-378.)Following chemical or mechanical injury, the liver has the extraordinary capacity to regenerate back to its normal mass within a short time. During regeneration, the same physiologic functions required by the organism must be performed with less metabolic "equipment," and therefore the liver must continuously adapt its metabolic output to its rapidly changing architecture. As a result of tissue loss, the concentrations of many factors, including growth factors, cytokines, and proteases, rise in the blood and liver to promote temporal and spatial proliferation and migration of the various cells to efficiently reconstitute the liver mass (reviewed by Michalopoulos 1 and Fausto 2 ). Following 70% partial hepatectomy (PHx) in the rat, hepatocyte DNA synthesis peaks abruptly at 24 hours after PHx, and essentially terminates DNA synthesis by 72 hours following resection. 3 Sinusoidal endothelial cells (SEC), the open, fenestrated, discontinuous endothelial cells that line the vessels supplying the parenchymal plates, do not initiate DNA synthesis until 48 to 72 hours after resection, peaking at 4 d post-PHx, but continue to proliferate at least until 8 days following PHx. [3][4][5] This cellular order of proliferative events results in the formation of avascular hepatic islands throughout the liver lobule. 6 Subsequent proliferation and migration of the sinusoidal endothelium i...

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Section: Ultrastructural Examination Of Sinusoids During Regenerationmentioning

confidence: 99%

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver

et al. 2001

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“…This stimulation of DNA synthesis by norepinephrine was strongly antagonised by the xl-adrenergic antagonist prazocin, but not by an M2-antagonist nor by a P-adrenergic blocker (Cruise et al, 1985). al-Adrenergic blockade, which affects both epidermal growth factor receptor binding and subsequent DNA synthesis in primary cultures of hepatocytes, can also modulate these processes during liver regeneration after partial hepatectomy (Cruise et al, 1987). Therefore, verapamil inhibits hepatocyte proliferation by antagonising a,-adrenoceptors and may inhibit proliferation of enzyme altered lesions and hepatocellular carcinomas induced by NNM by antagonising oa,-adrenoceptors.…”

Section: Discussionmentioning

confidence: 95%

Inhibition by verapamil of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats

Uehara

Nakaizumi²,

Baba³

et al. 1993

Br J Cancer

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Summary The effect of verapamil on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of verapamil or vehicle every other day for 16 weeks from the start of the experiment.Pre-neoplastic and neoplastic lesions staining positive for y-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 16. Prolonged administration of verapamil resulted in a significant decrease in the number of GGT-positive and GST-P-positive lesions. The incidence and volume as a percentage of parenchyma of hepatocellular carcinomas were also significantly less in rats treated with verapamil than in controls. Administration of verapamil significantly decreased the labelling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that verapamil inhibits hepatocarcinogenesis and that this may be related to its inhibitory effect on cell proliferation in neoplastic lesions and surrounding hepatocytes.

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“…1,3,29,30 Insulin, glucagon, noradrenalin, GH and thyroid hormones further regulate liver growth by enhancing the proliferative potential of mitogens, despite possessing little intrinsic mitogenic activity. 31,32 Growth factors play a major role in the maturation of organ systems prior to birth. 17 For example, in the fetus, IGFs, synthesized by the placenta and fetal liver, 33 mediate growth 34 under the regulation of glucose and insulin.…”

Section: Liver Regeneration and Hepatic Growth Control Mechanismsmentioning

confidence: 99%

Early developmental influences on hepatic organogenesis

2008

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The liver is the largest of the body's organs, with the greatest number of functions, playing a central role in coordinating metabolic homeostasis, nutrient processing and detoxification. The fetal liver forms during early gestation in response to a sequential array of distinct biological events, regulated by intrinsically programmed mechanisms and extracellular signals which instruct hepatic cells to either proliferate, differentiate or undergo apoptosis. A vast number of genes are involved in the initiation and control of liver development, many of which are sensitive to nutritional and hormonal regulation in utero. Moreover, liver mass is influenced by the gestational environment. Therefore, during periods of hepatic cell proliferation and differentiation, the developing fetal liver is sensitive to damage from both internal and external sources including teratogens, infection and nutritional deficiencies. For example, fetuses exposed to decreased materno-fetal nutrition during late gestation have a reduced liver mass, and/or perturbed liver function, which includes increased plasma LDL cholesterol and fibrinogen concentrations. These occur in conjunction with other risk factors present in the early stages of cardiovascular disease i.e. decreased glucose tolerance and insulin insensitivity in later life. Taken together, these findings suggest that liver mass, and later function, are essentially set in utero during fetal development-a process that is ultimately regulated by the intrauterine environment.

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α1-Adrenergic effects and liver regeneration

Cited by 189 publications

References 27 publications

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver

Inhibition by verapamil of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats

Early developmental influences on hepatic organogenesis

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