lisinopril and Reperfusion-Injury

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.. 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).. 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).. 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.

Topics: Alanine Transaminase; Angiotensin-Converting Enzyme Inhibitors; Animals; Endothelin-1; Lisinopril; Male; Models, Animal; Nitric Oxide; Peroxynitrous Acid; Rats; Reperfusion Injury; Superoxides

A number of studies have reported that oxidant stress reduces the activity of isolated Na(+)-K(+) ATPase and Ca(2+) ATPase which are known to affect the cell membrane integrity. The aim of the study is to determine whether the administration of lisinopril is able to protect the membrane-bound enzyme levels in isolated guinea pig hearts and also ascertain whether or not a relationship exists between oxygen free radicals and membrane bound Na(+)-K(+) ATPase and Ca(2+) ATPase. Forty guinea pig hearts were studied in an isolated Krebs-Henseleit solution-perfused Langendorff cardiac model. In all groups cardioplegic arrest was achieved by administering St. Thomas' Hospital cardioplegic solution (STHCS). Group 1 (control, n=10) received only STHCS. Group 2 (n=10) were arrested with lisinopril (l micromol l(-1)) added STHCS. Group 3 (n=10) were pretreated with oral lisinopril (0.2 mg kg(-1) twice a day) for 10 days and then arrested with STHCS. Group 4 were also pretreated with oral lisinopril (0.2 mg kg(-1) twice a day for 10 days), arrested with STHCS and reperfused with lisinopril added to Krebs-Henseleit solution (l micromol l(-1)). Hearts were subjected to normothermic global ischaemia for 90 min and then reperfused at 37 degrees C. Pretreatment and addition of lisinopril in the reperfusion buffer improved the levels of membrane-bound enzymes. When the treated groups were compared with control hearts, the best results were achieved in group 4. The Na(+)-K(+) and Ca(2+) ATPase levels increased from 466.38+/-5.99 to 560.12+/-18.02 and 884.69+/-9.13 to 1287.71+/-13.01 nmolPi mg(-1) protein h(-1) respectively (p<0.05). These results suggest that lisinopril protects the cell membrane integrity and lessens free radical-induced oxidant stress.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bicarbonates; Calcium Chloride; Calcium-Transporting ATPases; Glutathione; Guinea Pigs; Heart; Lisinopril; Magnesium; Membrane Proteins; Myocardial Ischemia; Myocardium; Oxidative Stress; Perfusion; Potassium Chloride; Reactive Oxygen Species; Reperfusion Injury; Sodium Chloride; Sodium-Potassium-Exchanging ATPase; Thiobarbituric Acid Reactive Substances; Time Factors

The present study was designed to investigate the effect of captopril, a sulfhydryl (-SH) containing ACE inhibitor and lisinopril, a non-SH containing ACE inhibitor, on ischaemia-reperfusion-induced renal injury in rats and to study the involvement of the free radical scavenging property of captopril in its renoprotective effect. Bilateral renal artery occlusion was induced for 30 min followed by reperfusion for 24 h. Blood samples were taken from retro orbital sinus before surgery and at 24 h after reperfusion for blood urea and blood creatinine estimation. After completion of 24 h of renal reperfusion the carotid artery was cannulated and the mean arterial blood pressure (MABP) was recorded. The left kidney was used for histological examination. The right kidney was utilised for estimation of mitochondrial thiobarbituric acid reactive substances (TBARS). Renal ischaemia, followed by reperfusion, significantly increased blood urea nitrogen (BUN) and blood creatinine. However, creatinine clearance decreased markedly. Captopril administered before renal artery occlusion or immediately after reperfusion and lisinopril pre-treatment significantly attenuated the increase in BUN and blood creatinine. Creatinine clearance was markedly better in captopril-treated animals as compared to lisinopril-treated rats. Captopril significantly decreased the degree of tubular necrosis, haemorrhagic streaks and urinary casts. Lisinopril treatment decreased tubular necrosis and urinary casts but no marked effect on haemorrhagic streaks was noted. Administration of captopril before ischaemia or just after reperfusion significantly reduced the elevated concentration of mitochondrial TBARS but no such decrease was noted in lisinopril-treated rats. Based on these results it may be concluded that captopril and lisinopril markedly protected against ischaemia-reperfusion-induced renal injury and any additional renoprotective effect of captopril may be ascribed to its free radical scavenging properties.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Female; Kidney; Lipid Peroxidation; Lisinopril; Male; Rats; Reperfusion Injury