Endothelin-1 induces cholestasis which is mediated by an increase in portal pressure

Carlos M Isales, Michael H. Nathanson, Rafael Bruck

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) is a potent vasoactive peptide which generally exerts its effect on target cells by increasing [Ca++]i. Both vasoconstriction (resulting in an increase in perfusion pressure) and increased [Ca++]i are actions of ET-1 that may result in cholestasis. Single-pass isolated perfused rat liver (IPRL) were used, and [Ca++]i was measured in both populations of hepatocytes and single cells. ET-1 (0.1-100 nM) induced a dose-dependent increase in perfusion pressure and decrease in bile flow. Perfusion pressure increased by 112% (p<0.001) and bile flow decreased by 17% (p<0.008) in response to 2 nM ET-1. At this concentration of ET-1, but not at higher concentrations, the cholestasis was abolished (p>0.18 vs basal) and the rise in perfusion pressure was decreased (by 62%; p<0.002) by the vasodilator papaverine. This ET-1 concentration also had no measurable effect on [Ca++]i in isolated hepatocytes. Taken together these findings indicate that ET-1 inhibits bile flow in IPRL and suggests that this effect is mediated by vasoconstriction and not by changes in hepatocyte cytosolic Ca++.

Original languageEnglish (US)
Pages (from-to)1244-1251
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume191
Issue number3
DOIs
StatePublished - Mar 31 1993
Externally publishedYes

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Portal Pressure
Cholestasis
Endothelin-1
Perfusion
Pressure
Hepatocytes
Vasoconstriction
Bile
Liver
Rats
Papaverine
Vasodilator Agents
Peptides
Population

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Endothelin-1 induces cholestasis which is mediated by an increase in portal pressure. / Isales, Carlos M; Nathanson, Michael H.; Bruck, Rafael.

In: Biochemical and Biophysical Research Communications, Vol. 191, No. 3, 31.03.1993, p. 1244-1251.

Research output: Contribution to journalArticle

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