Effect of angiotensin II and bradykinin inhibition in rat reduced-size liver transplantation.
This study examined whether angiotensin II (Ang II) blockers [Ang II type I receptor antagonist, Ang II type II receptor antagonist, and angiotensin converting enzyme (ACE) inhibitor] could reduce hepatic injury and improve regeneration in reduced-size orthotopic liver transplantation (ROLT) and whether the beneficial effects of ischemic preconditioning (PC) in ROLT could be explained by changes in Ang II. We show that small liver grafts generated Ang II after ROLT and that this was associated with increased angiotensinogen and ACE messenger RNA expression. Furthermore, inhibition of Ang II did not contribute to PC-induced protection in ROLT. All Ang II blockers reduced hepatic injury, but none of them promoted liver regeneration. Bradykinin (BK) receptor antagonist improved liver regeneration but did not reduce hepatic injury in ROLT. Finally, the combination of Ang II blockers and BK receptor antagonists in ROLT reduced hepatic injury and improved liver regeneration. In conclusion, treatments with either Ang II blockers or BK receptor antagonists cannot, on their own, improve the outcome of ROLT. Although Ang II blockers can reduce hepatic ischemia-reperfusion injury and BK receptor antagonists can promote liver regeneration, neither confers both benefits at the same time. Consequently, it may be of clinical interest to apply both treatments simultaneously.
Padrissa-Altés
Susagna
S
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Cientícas, Barcelona, Spain.
Franco-Gou
Rosa
R
Boillot
Olivier
O
Serafín
Anna
A
Rimola
Antoni
A
Arroyo
Vicente
V
Rodés
Joan
J
Peralta
Carmen
C
Roselló-Catafau
Joan
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006499:Hepatic Artery / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology*; D008102:Liver Circulation; D016031:Liver Transplantation / Q000379:methods* / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D016133:Polymerase Chain Reaction; D011169:Portal Vein / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012038:Regeneration
D057912:Angiotensin II Type 2 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D018809:Proliferating Cell Nuclear Antigen; D011725:Pyridines; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; C073402:PD 123319; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin