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Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease.

ABSTRACT: Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage with carbon tetrachloride (CCl4). Portal pressure was recorded acutely during intravenous infusion of endothelin receptor antagonists in normal or portal hypertensive mice. In vivo microscopy was used to monitor sinusoidal dynamics. Additionally, the effect of chronic exposure to endothelin antagonists was assessed in mice during induction of fibrosis and cirrhosis with CCl4 for 8 wk. Intravenous infusion of ET-A receptor antagonists into normal and cirrhotic mice reduced portal pressure whereas ET-B receptor antagonism increased portal pressure. A mixed endothelin receptor antagonist also significantly reduced portal pressure. Additionally, the ET-A receptor antagonist caused sinusoidal dilation, whereas the ET-B receptor antagonist caused sinusoidal constriction. Chronic administration of each the endothelin receptor antagonists during the induction of fibrosis and portal hypertension led to reduced fibrosis, a significant reduction in portal pressure, and altered sinusoidal dynamics relative to controls. Acute effects of endothelin receptor antagonists are likely directly on the hepatic and sinusoidal vasculature, whereas chronic endothelin receptor antagonism appears to be more complicated, likely affecting fibrogenesis and the hepatic microcirculation. The data imply a relationship between hepatic fibrogenesis or fibrosis and vasomotor responses.

SUBMITTER: Feng HQ

PROVIDER: S-EPMC2711758 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease.

Feng Hong-Qiang HQ Weymouth Nate D ND Rockey Don C DC

American journal of physiology. Gastrointestinal and liver physiology 20090319 1

Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage wit ...[more]

PMID: 19299580

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Project description:Background:Portal hypertensive polyps in patients with portal hypertension are described. Aims:The most significant and serious complication in liver cirrhosis proves to be portal hypertension. Polypoid lesions, which can be seen in the stomach as endoscopic finding in patients with portal hypertension, have not quite been defined in the literature. The aim of this study, therefore, was to define polypoid lesion formation due to portal hypertension in the upper gastrointestinal system in patients with portal hypertension. Study Design. Cross-sectional study. Methods:The study covered a group of patients with liver cirrhosis and a healthy control group that did not have portal hypertension. All individuals covered by the study received upper GI endoscopy, while the endoscopic features and pathological characteristics of the identified polypoid lesions were defined. Standard histological criteria were used in polyp diagnosis. Results:A total of 400 individuals were included in the study. Upper GI endoscopy was performed for 200 patients with liver cirrhosis and another 200 healthy individuals with no portal hypertension in the control group. When the cases were gastroscopically assessed with regard to polypoid lesion presence, it was seen that a total of 87 (21.8%) individuals had polyps. While 67 (33.5%) cirrhotic patients were identified to have polyps, 20 (10%) individuals in the healthy control group had polyps. When the results of those with liver cirrhosis who received esophageal variceal endoscopic band ligation (EVL) and who did not were compared, it was observed that a higher number of individuals in the group with EVL had polypoid lesions. When the patient and control groups were compared as to Helicobacter pylori presence, the results showed that it was slightly higher in the dyspepsia group but the difference was not statistically significant (p > 0.05). Conclusion:Portal hypertension-associated polypoid lesions are common in advanced liver cirrhosis cases. The pathological analyses of these polyps pointed out that they were all benign and no malignant cases were detected. It was argued that these polypoid lesions, referred to as portal hypertensive polyps, were associated with elevated angiogenesis in the gastric mucosa.

Dataset Information

Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease.

Publications

Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease.

Similar Datasets

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