title: Inhibition of angiotensin-converting enzyme reduces rat liver reperfusion injury via bradykinin-2-receptor.
abstract: BACKGROUND
  Bradykinin is both a potent vasodilatator and a central inflammatory mediator. Similar to findings in myocardial reperfusion injury, bradykinin might mediate the protective effects of angiotensin-converting enzyme (ACE) inhibition after liver ischemia via increased bradykinin-2-receptor (B-2) stimulation. On the other hand, B-2-inhibition has been shown to reduce liver reperfusion injury. This study was designed to investigate the role of Bradykinin in hepatic reperfusion injury.
  
  
  METHODS
  Twenty eight rats were allocated randomly to Sham procedure (Sham), 30-min normothermic ischemia (ischemia), ischemia with Ramiprilat (ACE-I), or ischemia with Ramiprilat and B-2-inhibitor HOE 140 (ACE-I+B-2-I). Liver microcirculation and leukocyte adherence were investigated using intravital microscopy 30 min after reperfusion (n = 7 per group). In addition, serum activities of AST and ALT were measured for 7 days (n = 28).
  
  
  RESULTS
  Ischemia was associated with a loss of perfused sinusoids, sinusoidal vasoconstriction, and a reduction in microvascular blood flow. Permanent leukocyte adherence increased both in sinusoids and in postsinusoidal venoles. ACE-I restored sinusoidal perfusion, normalized vasoregulation, maintained sinusoidal blood flow, and inhibited leukocyte adhesion. ACE-I+B-2-I abolished the protective effects linked to ACE-I. Ischemia-induced liver cell injury after 5 h of reperfusion was ameliorated by ACE-I. In the ACE-I+B-2-I group, reduction in liver cell injury was reversed.
  
  
  CONCLUSIONS
  After hepatic ischemia, ACE-I reduced reperfusion injury in a B-2-dependent manner. These results suggest a pivotal role for bradykinin in the treatment of reperfusion injury by Ramiprilat, mediating sinusoidal dilation and blunting hepatic inflammation.
authors.affiliation: Department of General Surgery, Surgical Research, University Hospital Muenster, Muenster, Germany. freiseh@uni-muenster.de
authors.forename: Hendrik
authors.initials: H
authors.lastname: Freise
authors.forename: Daniel
authors.initials: D
authors.lastname: Palmes
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Spiegel
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D065094:Bradykinin B2 Receptor Antagonists; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D007511:Ischemia; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008833:Microcirculation / Q000503:physiopathology; D017257:Ramipril / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014661:Vasoconstriction
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; D043782:Receptor, Bradykinin B2; C052549:ramiprilat; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin