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.