Effect of angiotensin-converting enzyme inhibitors on liver regeneration in rats.
OBJECTIVE
We previously reported that bradykinin augments liver regeneration in rats. The angiotensin-converting enzyme is also a powerful bradykinin-degrading enzyme.


METHODS
Adult rats received lisinopril, captopril, enalaprilat, or saline solution, intraperitoneally, for 5 days before 70% partial hepatectomy, and daily after surgery. They received also losartan and 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 points after hepatectomy, except 120 hours. The remnant liver dry weight was higher in lisinopril-treated rats 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 losartan induced a lower hepatocyte labeling index in comparison to the control group at 36 hours after hepatectomy.


CONCLUSIONS
The present results provide evidence that angiotensin-converting enzyme inhibitors remarkably enhance liver regeneration.
Ramalho
Fernando S
FS
Department of Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo 14049-900, Ribeirão Preto, SP, Brazil.
Ramalho
Leandra N Z
LN
Castro-e-Silva Júnior
Orlando
O
Zucoloto
Sérgio
S
Corrêa
Fernando M A
FM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D017706:Lisinopril / Q000494:pharmacology*; D008115:Liver Regeneration / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009929:Organ Size; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D002216:Captopril; D017706:Lisinopril; D015773:Enalaprilat; D019808:Losartan