Angiotensin-converting enzyme inhibition by lisinopril enhances liver regeneration in rats

Bradykinin has been reported to act as a growth factor for fibroblasts, mes angial cells and keratinocytes, Recently, we reported that bradykinin augme nts liver regeneration after partial hepatectomy in rats. Angiotensin-conve rting enzyme (ACE) is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regenerati on after partial hepatectomy. Adult male Wistar rats underwent 70% partial hepatectomy (PH). The animals received lisinopril at a dose of 1 mg kg body weight(-1) day(-1), or saline solution, intraperitoneally, for 5 days befo re hepatectomy, and daily after surgery. Four to six animals from the lisin opril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h af ter PH. Liver regeneration was evaluated by immunohistochemical staining fo r proliferating cell nuclear antigen using the PC-IO monoclonal antibody. T he value for the lisinopril-treated group was three-fold above the correspo nding control at 12 h after PH (P<0.001), remaining elevated at approximate ly two-fold above control values at 24, 36, 48 (P<0.001), and at 72 h (P<0. 01) after PH, but values did not reach statistical difference at 120 h afte r PH. Plasma ACE activity measured by radioenzymatic assay was significantl y higher in the saline group than in the lisinopril-treated group (P<0.001) , with 81% ACE inhibition. The present study shows that plasma ACE inhibiti on enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors.