Effect of angiotensin-converting enzyme inhibitors on liver regeneration in rats

Background/Aims: We previously reported that bradykinin augments liver regeneration in rats. The angiotensin-converting enzyme is also a powerful bradykinin-degrading enzyme. Methodology: Adult rats received lisinopril, captopril, enbalaprilat, or saline solution, intraperitoneally, for 5 days before 70% partial hepatectomy, and daily after surgery. They received also losartan anti bradykinin. Rats were sacrificed at 12, 24, 36, 48, 72, and 120 hours after hepatectomy. Liver regeneration was evaluated in terms of the restoration of liver weight in proportion to body weight, liver DNA content and immunostaining for proliferating cell nuclear antigen. Results: The proliferating cell nuclear antigen labeling index was higher in the lisinopril-treated group than in the control group at all time point after hepatectomy, except 120 hours. The remnant liver dry weight was higher in lisinopril-treated rate than in control rats at early time points after surgery. The liver DNA content was higher in three angiotensin-converting enzyme inhibitor-treated groups than in the control group at 36 hours after hepatectomy. The bradykinin-induced regenerative response was similar to the lisinopril-induced response, and lossartan induced a lower hepatocyte labeling index in comparison to the control group at 36 hows after hepatectomy. Conclusions: The present results provide evidence that angiotensin-converting enzyme inhibitors remarkably enhance liver regeneration.