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). Conclusion. 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.