Endotoxin and the hyperdynamic circulation of portal vein—ligated rats

Mehta, Rajeev; Gottstein, Jeanne; Zeller, W. Patrick; Lichtenberg, Robert; Blei, Andrés T.

doi:10.1002/hep.1840120513

Cited by 24 publications

(5 citation statements)

References 25 publications

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“…In addition, we could not detect circulating endotoxin in these animals. Although circulating endotoxin is present in rats within hours after portal vein ligation, it appears to be absent in rats subjected to portal vein constriction for long periods (19,20,21). It is therefore unlikely that chronic endotoxemia is responsible for the hyperdynamic circulation seen in this animal model.…”

Section: Discussionmentioning

confidence: 82%

Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats

Karatapanis¹,

McCormickM.D.MRCP²,

Kakad³

et al. 1994

Hepatology

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It has been suggested that increased production of nitric oxide by an inducible nitric oxide synthase isoenzyme is important in the pathogenesis of the vascular abnormalities seen in human beings and animals with portal hypertension. We investigated this hypothesis by studying the in vitro vascular reactivity of isolated aortic rings from portal vein-constricted and sham-operated rats. Aortic rings from portal vein-constricted rats exhibited significantly impaired contractility to phenylephrine and potassium chloride compared with control rats. Preincubation with the nitric oxide synthase inhibitor nitro-L-arginine methyl ester significantly increased contractility to phenylephrine and potassium chloride in both portal-hypertensive and control tissues, with greater effect in the portal-hypertensive rings. Despite nitro-L-arginine methyl ester, maximal contractions were still significantly smaller in the portal-hypertensive tissues. Vascular relaxation evoked by acetylcholine, but not by the endothelium-independent vasodilator glyceryl trinitrate, was significantly impaired in the portal-hypertensive group. Our results demonstrate significant impairment in vascular function in aortic rings in this model of portal hypertension. The addition of a nitric oxide synthase inhibitor partly corrected these changes, suggesting that although nitric oxide is likely an important mediator, other factors may also be involved in the pathogenesis of these alterations in vascular function.

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Section: Discussionmentioning

confidence: 82%

Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats

Karatapanis¹,

McCormickM.D.MRCP²,

Kakad³

et al. 1994

Hepatology

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“…Moreover, elevated levels of TNF have been reported in various models of rats with liver cirrhosis, (36) which appear to be most pronounced and mainly gut derived in the advanced stage (37), known to be associated with the presence of BT. It is important to emphasize that particularly in the early phase after PVL but not or far less in long‐standing PVL animals' enhanced serum levels of TNF and endotoxins have been demonstrated (36, 38). It is therefore tempting to speculate that these high levels of, e.g., TNF and endotoxins released from the gut and its associated lymphatic tissue in response to BT are responsible for the increased PMNL phagocytic activity in portal‐hypertensive animals.…”

Section: Discussionmentioning

confidence: 99%

Bacterial translocation increases phagocytic activity of polymorphonuclear leucocytes in portal hypertension: priming independent of liver cirrhosis

Neugebauer

Hartmann

Krenn

et al. 2008

Liver International

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“…NO may act as a messenger molecule for LPS and cytokine-induced cGMP biosynthesis in liver cells (34). Endotoxins have not been detected in arterial samples of PVL rats (35). However, the hypothesis that endotoxin does play a role in the hyperdynamic circulation of this experimental model cannot be completely ruled out.…”

Section: Discussionmentioning

confidence: 82%

Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites.

López-Talavera

Levitzki²,

Martinez³

et al. 1997

J. Clin. Invest.

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Tumor necrosis factor-␣ (TNF) causes vasodilatation and a hyperdynamic state by activating nitric oxide (NO) synthesis. Tyrphostins, specific inhibitors of protein tyrosine kinase (PTK), block the signaling events induced by TNF and NO production. A hyperdynamic circulatory syndrome (HCS) is often observed in portal hypertension (PHT). TNF and NO seem to mediate these hemodynamic changes. The aim of this work was to study the effect of PTK inhibition on the systemic and portal hemodynamics, TNF and NO production, in cirrhotic rats with portal hypertension. Rats with liver cirrhosis induced by chronic inhalation of carbon tetrachloride were used. Animals were treated daily with tyrphostin AG 126 ( ␣ -cyano-(3-hydroxy-4-nitro) cinnamonitrile) or placebo for 5 d. Mean arterial pressure (MAP), heart rate (HR), and portal pressure (PP) were measured by indwelling catheters. Cardiac output (CI) and stroke volume (SV) were estimated by thermodilution, systemic vascular resistance (SVR) was calculated (MAP/CI), and portal systemic shunting (PSS) was quantitated using radioactive microspheres. Serum and mesenteric lymph node (MLN) TNF levels were measured using an immunoassay kit, and serum NOx was determined photometrically by its oxidation products. The AG 126-treated group showed a statistically significant increase in MAP and SVR, and decreases in CI, SV, MLN TNF, and serum NO oxidation products nitrite and nitrate (NOx) in comparison with the placebotreated rats. No significant differences were noticed in HR, PP, PSS, or serum TNF. Significant correlations were observed between MAP and NOx, MAP and MLN TNF, PSS and NOx, and serum TNF and serum NOx. The HCS observed in PHT seems to be mediated, at least in part, by TNF and NO by the activation of PTKs and their signaling pathways. PTK activity inhibition ameliorates the hyperdynamic abnormalities that characterize animals with cirrhosis and PHT. ( J. Clin. Invest. 1997. 100:664-670.)

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Endotoxin and the hyperdynamic circulation of portal vein—ligated rats

Cited by 24 publications

References 25 publications

Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats

Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats

Bacterial translocation increases phagocytic activity of polymorphonuclear leucocytes in portal hypertension: priming independent of liver cirrhosis

Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites.

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