Liver Biology and Pathobiology

You have full text access to this OnlineOpen article

Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver

  1. Hauke Rensing1,
  2. Inge Bauer M.D.1,*,
  3. Jian X. Zhang2,
  4. Markus Paxian1,
  5. Benedikt H. J. Pannen3,
  6. Yukihiro Yokoyama2,
  7. Mark G. Clemens2,
  8. Michael Bauer1

Article first published online: 7 MAR 2007

DOI: 10.1002/hep.1840360623

Issue

Hepatology

Hepatology

Volume 36, Issue 6, pages 1453–1465, December 2002

Additional Information

How to Cite

Rensing, H., Bauer, I., Zhang, J. X., Paxian, M., Pannen, B. H. J., Yokoyama, Y., Clemens, M. G. and Bauer, M. (2002), Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver. Hepatology, 36: 1453–1465. doi: 10.1002/hep.1840360623

Author Information

  1. 1

    Department of Anesthesiology and Critical Care Medicine, University of the Saarland, Homburg, Germany

  2. 2

    Department of Biology, University of North Carolina at Charlotte, Charlotte, NC

  3. 3

    Department of Anesthesiology and Critical Care Medicine, University of Freiburg, Freiburg, Germany

*Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, D-66421 Homburg/Saar, Germany. fax: (49) 6841–16–22833

Publication History

  1. Issue published online: 7 MAR 2007
  2. Article first published online: 7 MAR 2007
  3. Manuscript Accepted: 7 SEP 2002
  4. Manuscript Received: 19 FEB 2002

Funded by

  • Deutsche Forschungsgemeinschaft. Grant Numbers: Ba-1601/1–2, PA 533/2–3, PA 533/3–1

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (1361K)

Abstract

Heme oxygenase (HO)-1 is up-regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO-1 leads to an increased portal pressor response in the stress-exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up-regulation of the vasoconstrictor endothelin (ET)-1. Hemorrhagic shock induced messenger RNAs encoding HO-1 (16-fold) and ET-1 (9-fold) with a similar time course in the liver. At maximum induction of both mediators, rats received either vehicle or the endothelin ETA/B antagonist bosentan (10 mg/kg intravenously). Subsequently, the HO pathway was blocked in all animals by tin-protoporphyrin (SnPP)-IX (50 μmol/kg intravenously). Portal and sinusoidal hemodynamics were measured using microflow probes and intravital microscopy, respectively. Blockade of the HO pathway led to a significant increase in portal resistance (sham/SnPP-IX, 0.17 ± 0.046 mm Hg · min · mL−1; shock/vehicle/SnPP-IX, 0.57 ± 0.148 mm Hg · min · mL−1; P < 0.05) and a decrease in sinusoids conducting flow (shock/vehicle/SnPP-IX: baseline, 28.3 ± 0.85 sinusoids/mm; 10 minutes after SnPP-IX, 23.1 ± 1.09 sinusoids/mm; P < 0.05). Intravital microscopy showed narrowing of failing sinusoids colocalizing with stellate cells after blockade of the HO pathway. Blockade of ETA/B receptors attenuated the increase in portal resistance (shock/bosentan/SnPP-IX, 0.29 ± 0.051 mm Hg · min · mL−1) and prevented sinusoidal perfusion failure (shock/bosentan/SnPP-IX: baseline, 28.2 ± 0.97 sinusoids/mm; 10 minutes after SnPP-IX, 28.8 ± 1.18 sinusoids/mm) as well as sinusoidal narrowing. In conclusion, a functional interaction of the up-regulated vasodilatory HO system and the vasoconstrictor ET-1 on the sinusoidal level exists under stress conditions. Both mediator systems affect sinusoidal diameter via direct action on hepatic stellate cells in vivo. (HEPATOLOGY2002;36:1453–1465).

Get PDF (1361K)