title: Lisinopril inhibits endothelin-1 in the early period of hepatic reperfusion injury in a partial hepatectomy model.
abstract: BACKGROUND
  Ischemia-reperfusion (I/R) injury is a major problem during liver surgery. We investigated the effects of lisinopril, an angiotensin-converting enzyme inhibitor, in the early postoperative period of reperfusion injury after Pringle's maneuver during an 80% partial hepatectomy (PH) in rats.
  
  
  METHODS
  Four groups of male Sprague-Dawley rats were studied: Group 1 (n = 10), sham laparotomy; group 2 (n = 10), PH without portal occlusion; group 3 (n = 10), PH with portal pedicle clamping; group 4 (n = 15), same as group 3 with additional intravenous lisinopril preconditioning (1 mg/kg(-1)). We analyzed superoxide radical (O(2)(-)), nitric oxide (NO), peroxynitrite (ONOO(-)) levels in the liver tissue and blood levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1).
  
  
  RESULTS
  ALT and ET-1 levels were progressively increased in group 2 (P > .05) versus group 3 (P < .001 and P < .05), showing hepatocellular damage due to I/R injury in the remnant liver, although histopathologic changes were unremarkable at this early stage. The levels of ALT and ET-1 decreased with lisinopril precontioning in group 4 compared with group 2 (P > .05 and P < .01) or group 3 (P < .05 and P < .001). O(2)(-) levels were increased significantly in groups 2 and 3 (P < .01 for both). O(2)(-) level in Group 4 was remarkably decreased albeit not significant compared with the other groups. NO and ONOO(-) levels were also significantly greater in groups 2 (P < .01 and P < .05) and 3 (P < .001 and P < .01). These levels were decreased significantly among group 4 compared with group 3 (P < .05), a decline almost to the level of group 1 (P > .05).
  
  
  CONCLUSIONS
  In the early postoperative period of an extended hepatectomy model, Pringle's maneuver causes I/R increasing the insult to the remnant liver. Lisinopril preconditioning alleviated I/R injury by decreasing the O(2)(-), NO, ONOO(-), ET-1, and ALT levels, thereby exerting a protective role on the remaining liver.
authors.affiliation: Department of Surgery, Kocaeli University Hospital, Kocaeli, Turkey.
authors.forename: O A
authors.initials: OA
authors.lastname: Yirmibeşoğlu
authors.forename: O
authors.initials: O
authors.lastname: Büyükgebiz
authors.forename: D
authors.initials: D
authors.lastname: Ars
authors.forename: O
authors.initials: O
authors.lastname: Unay
authors.forename: D
authors.initials: D
authors.lastname: Cevik
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000097:blood; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury; D013481:Superoxides / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D017706:Lisinopril; D000410:Alanine Transaminase