Endothelin-A receptor blockade improves postischemic hepatic microhemodynamics.

Abstract

The aim of this study was to investigate a possible protective role of a selective endothelin-A receptor antagonist on hepatic microcirculation after ischemia/reperfusion. In a rat model, warm ischemia of the left liver lobe was induced for 90 minutes under intraperitoneal anesthesia with xylazine and ketamine. Shamoperated and untreated ischemic groups and a group treated with BSF 208075 were investigated. The effect of the endothelin-A receptor antagonist on ischemia/reperfusion was assessed by in-vivo microscopy and measurement of aspartate aminotransferase and alanine aminotransferase levels. In the untreated group, sinusoidal constriction to 70% of basal diameters was observed, leading to a significant decrease in perfusion rate. In addition, we found an increased percentage of stagnant leukocytes and platelets in sinusoids and in postsinusoidal venules (P < 0.05). A significant increase in liver enzymes was detected 6 hours after reperfusion (P < 0.05). In the treatment group, sinusoidal diameters were maintained at 108%, and perfusion rate was significantly increased (P < 0.05). Hepatocellular damage was decreased and leukocyte and platelet-endothelium interactions were reduced (P < 0.05). Our results provide evidence that the new therapeutic approach using an endothelin-A receptor antagonist is effective in reducing hepatic ischemia/reperfusion injury. It could be shown for the first time that endothelin receptor blockade also influences platelet-endothelium interactions.

• Authors: Dirk Uhlmann, Sebastian Glasser, Heike Lauer, Stefan Ludwig, Gabor Gaebel, Frederick Serr, Johann Hauss, Helmut Witzigmann
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 44 Suppl 1 Pg. S103-4 (Nov 2004) ISSN: 1533-4023 [Electronic] United States
• PMID: 15838253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiovascular Agents
• Endothelin A Receptor Antagonists
• Endothelin-1
• Phenylpropionates
• Pyridazines
• Receptor, Endothelin A
• Aspartate Aminotransferases
• Alanine Transaminase
• ambrisentan

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Cardiovascular Agents (pharmacology)
• Disease Models, Animal
• Endothelin A Receptor Antagonists
• Endothelin-1 (metabolism)
• Endothelium, Vascular (drug effects, metabolism, physiopathology)
• Female
• Hemodynamics (drug effects)
• Leukocyte Rolling (drug effects)
• Liver (blood supply, enzymology)
• Liver Circulation (drug effects)
• Microcirculation (drug effects, physiopathology)
• Microscopy, Fluorescence
• Microscopy, Video
• Phenylpropionates (pharmacology)
• Platelet Adhesiveness (drug effects)
• Pyridazines (pharmacology)
• Rats
• Rats, Wistar
• Receptor, Endothelin A (metabolism)
• Reperfusion Injury (metabolism, physiopathology, prevention & control)