Endothelin A—receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis

Nishida, Toshirou; Huang, Taiping; Seiyama, Akitoshi; Hamada, Etsuo; Kamiike, Wataru; Ueshima, Shigeyuki; Kazuo, Hiromu; Matsuda, Hikaru

doi:10.1016/s0016-5085(98)70208-2

Cited by 24 publications

(16 citation statements)

References 23 publications

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“…The ET B mRNA transcripts were potentiated in the animals subjected to trauma prior to a septic challenge, suggesting that trauma primes the host for an enhanced ET B mRNA gene expression. Ruetten and Thiemermann [18] observed a reduced hepatocellular injury in endotoxemic rats treated with ET B but not ET A receptor antagonists, and Nishida et al [19] noted aggravated endotoxin-induced hepatic injury in rats treated with selective ET A receptor antagonists. Thus, the effects of endothelin on the liver are complex and heterogenous and may vary between experimental models and species.…”

Section: Discussionmentioning

confidence: 98%

Role of Kupffer Cells in Vascular Stress Genes During Trauma and Sepsis

Lee

Clemens

Lee

2010

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 98%

Role of Kupffer Cells in Vascular Stress Genes During Trauma and Sepsis

Lee

Clemens

Lee

2010

Journal of Surgical Research

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“…disturb hepatic microcirculation and worsen endotoxininduced liver injury, 37 while chronic blockade with a mixed antagonist Bosentan had no hemodynamic effects but increased the connective tissue content of cirrhotic liver. 38 Thus, precise elucidation of ETR, especially ETBR-mediated paracrine/autocrine functions of ET is required to understand the role of ET and its antagonists or agonists.…”

Section: Discussionmentioning

confidence: 98%

Enhanced expression of endothelin B receptor at protein and gene levels in human cirrhotic liver

Yokomori¹,

Oda²

2001

Gastroenterology

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“…30 On the other hand, our results obtained with this non-selective ETA and ETB receptor antagonist differ from those obtained with a selective ETA receptor antagonist which showed worsening of endotoxin induced hepatic changes and necrosis. 31 This suggests that endothelin via ETB receptors or the association of both ET receptors plays a major role in the occurrence of liver injury following LPS administration.…”

Section: Discussionmentioning

confidence: 99%

Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats

Urbanowicz

Sogni²,

Moreau³

et al. 2004

Gut

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Background/aims: Lipopolysaccharide (LPS ) induces liver injury which is associated with upregulated endothelin (ET)-1 production. The aim of this study was to investigate the effects of tezosentan, a nonselective ETA and ETB receptor antagonist, in LPS challenged rats with cirrhosis. Methods: Rats with cirrhosis received LPS and then tezosentan or placebo one hour later. Four hours after LPS administration, rats were killed to measure serum transaminase activity and plasma tumour necrosis factor a (TNF-a) levels. Hepatic inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), a marker of neutrophil infiltration, and cyclooxygenase (COX)-2 expression were also measured. Results: LPS administration significantly decreased arterial pressure and significantly increased plasma endothelin levels. Following LPS and tezosentan administration, serum aspartate aminotransferase and alanine aminotransferase activities were similar to those in the control group while they were increased by more than 700% with LPS alone. Plasma TNF-a levels were significantly lower in rats receiving LPS and tezosentan (182 (38) pg/ml) compared with those receiving LPS alone (821 (212) pg/ml). Tezosentan significantly decreased hepatic MPO activity and hepatic neutrophils but had no effect on LPS induced iNOS or COX-2. Survival rate was significantly higher in rats receiving LPS plus tezosentan (80%) than in rats receiving LPS alone (50%). Conclusion: In LPS challenged cirrhotic rats, tezosentan administration prevents LPS induced liver injury by decreasing intrahepatic neutrophil infiltration. In addition, tezosentan increases survival in these rats.

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Endothelin A—receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis

Cited by 24 publications

References 23 publications

Role of Kupffer Cells in Vascular Stress Genes During Trauma and Sepsis

Role of Kupffer Cells in Vascular Stress Genes During Trauma and Sepsis

Enhanced expression of endothelin B receptor at protein and gene levels in human cirrhotic liver

Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats

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