Gene Expression of Endothelin-1 and ET&lt;sub&gt;A&lt;/sub&gt; and ET&lt;sub&gt;B&lt;/sub&gt; Receptors in Human Cirrhosis: Relationship with Hepatic Hemodynamics

Leivas, Albert; Jiménez, Wladimiro; Bruix, Jordi; Boix, Loreto; Bosch, Jaime; Arroyo, Vicente; Rivera, Francisca; Rodés, Joan

doi:10.1159/000025583

Cited by 87 publications

(61 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous endothelin studies that investigated this issue mainly focused on the resistance of portal vein or intrahepatic vasculature. 5,[13][14][15]30 Recently, indirect evidence regarding the effect of ET-1 on the collateral vascular resistance was reported by Sogni et al 15 They found that in vivo infusion of bosentan, a mixed ET A and ET B receptor antagonist, significantly reduced the portal pressure and hepatocollateral resistance in PVL and cirrhotic rats. 15 Because bosentan had no effect on the intrahepatic vascular resistance in normal rats, they proposed that in PVL rats bosentan must decrease the collateral vascular resistance.…”

Section: Discussionmentioning

confidence: 97%

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats

et al. 2001

View full text Add to dashboard Cite

Cirrhosis of liver leads to portal hypertension and the development of portal-systemic collaterals. 10 The increased hepatic and collateral resistances to an increased portal blood flow maintain portal hypertension. 11 Recently, a possible role of endothelins in the pathophysiology of portal hypertension has been suggested. ET-1 was found to induce hepatic vasoconstriction and subsequently increase portal venous resistance. 4,12 In addition, ET-1 could stimulate contraction of hepatic stellate cells to increase intrahepatic resistance. 13 In vitro experiments also showed that ET-1 produced contraction of rat portal vein. 14 Furthermore, the mesenteric expressions of ET A and ET B receptors and ET-1-induced vasoconstriction were significantly enhanced in partially portal veinligated (PVL) rats. 5 Recently, it has been shown that bosentan, a nonselective endothelin receptor antagonist, significantly reduced the portal pressure of portal hypertensive rats. 15 However, it is not clear if ET-1 could modulate portal pressure by a direct constrictive effect on the collateral vessels of portal hypertensive rats.The aims of this study were to investigate the vascular activity and the receptor-mediated effects of ET-1 on the portalsystemic collaterals of portal hypertensive rats. The regulation of nitric oxide (NO) and prostaglandin on the effects of ET-1 was also evaluated. MATERIALS AND METHODSMale Sprague-Dawley rats weighing 280 to 300 g at the time of surgery were used for experiments. The rats were housed in a plastic cage and allowed free access to food and water. All rats were fasted for 12 hours before operation. In all experiments, the investigators adhered to the American Physiological Society Guiding Principles for the Care and Use of Laboratory Animals.A prehepatic portal hypertensive animal model was created as previously reported. 16 Anesthesia was performed with ketamine HCl (100 mg/kg body weight, intramuscularly). In brief, the portal vein was isolated and a 3-0 silk ligature was tied around both the portal vein and an adjacent 20-gauge blunt-tipped needle. The needle was then removed and the vein allowed to reexpand. A second loose ligature was left around the portal vein with 2 endings of the ligature placed on each side in the abdominal cavity. The abdomen was then closed and the animal was allowed to recover. Perfusion studies were performed in overnight-fasted rats 10 to 13 days after the operation, at which time an extensive collateralization of the portal system was fully established. 17 The body weights of rats were measured on the day of perfusion studies.Abbreviations: ET-1, endothelin-1; PVL, portal vein-ligated; NO, nitric oxide; NNA, n -nitro-L-arginine; INDO, indomethacin.From the Divisions of

show abstract

Section: Discussionmentioning

confidence: 97%

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats

et al. 2001

View full text Add to dashboard Cite

show abstract

“…44 Indeed, localization of infused, labeled ET-1 in the liver is consistent with binding to stellate cells. 15,45 Further, endothelin receptors are up-regulated in the injured liver 40,46 and specifically in stellate cells 19 (Fig. 1).…”

mentioning

confidence: 89%

Vascular mediators in the injured liver

2003

View full text Add to dashboard Cite

“…Diastolic dysfunction, characterized by an altered pattern of transmitral flow due to impaired diastolic relaxation of left ventricle, can be easily assessed by echocardiography and accordingly can be considered as a marker of this condition. As far as diastolic dysfunction is concerned, many etiological factors have been reliably advocated as potential pathogenic agents: notably substances as NO [18][19][20][21], TNF [22], reactive nitrogen species [23], neurohormones [24][25][26][27][28] may well affect heart structure and function along with circulatory overload [24,29] and overactivity of the SNS [30]. Thickening of heart parietal walls has been reported [12,14,17,31], nevertheless the nature of the structural changes underlying diastolic dysfunction has not been clarified so far.…”

Section: Introductionmentioning

confidence: 99%

Heart Function and Myocardial Tissue Characterization in Patients with HCV Related Cirrhosis: Diastolic Dysfunction and Cardiac Hypertrophy

Pozzi¹,

Pizzala²,

Ratti³

et al. 2007

TOGASJ

View full text Add to dashboard Cite

Evidence of diastolic dysfunction in cirrhosis contributed to the definition of cirrhotic cardiomyopathy. In 109 patients with chronic HCV infection with or without cirrhosis E/A ratio, a Doppler marker of diastolic dysfunction, was decreased in cirrhotics (0.89 ± 0.03 vs controls 1.21 ± 0.07, p < 0.01) and to a lesser extent in patients with advanced liver fibrosis (1.17 ± 0.07, p < 0.01). Left ventricular parietal wall thickness was increased. The nature of this abnormality in human cirrhosis has not been clarified, animal studies reporting cardiac hypertrophy. To this aim we employed the echocardiographic integrated backscatter (IBS) technique to obtain an indirect estimate of tissue density (decreased when a higher percentage of muscle fibres is present and increased when fibrosis prevails) to provide myocardial tissue characterization in a subset of patients with compensated HCV cirrhosis. The average IBS signal was reduced in cirrhotics at the level of the posterior wall (21.72 ± 1.46 dB versus 30.85 ± 1.40 dB in controls, p < 0.01). Our results confirm diastolic dysfunction in postviral cirrhosis pointing to cardiac hypertrophy as the anatomopathological background in the compensated stage of disease.

show abstract

Gene Expression of Endothelin-1 and ET<sub>A</sub> and ET<sub>B</sub> Receptors in Human Cirrhosis: Relationship with Hepatic Hemodynamics

Cited by 87 publications

References 22 publications

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats

Endothelin-1 induces vasoconstriction on portal-systemic collaterals of portal hypertensive rats

Vascular mediators in the injured liver

Heart Function and Myocardial Tissue Characterization in Patients with HCV Related Cirrhosis: Diastolic Dysfunction and Cardiac Hypertrophy

Contact Info

Product

Resources

About