Effect of adrenomedullin on hepatic damage in hepatic ischaemia/ reperfusion injury in rats

Aims: Adrenomedullin (AM) is a multifunctional peptide with a putative beneficial role after an ischaemic insult. The aim of this study was to evaluate the effect of AM on partial hepatic ischaemia reperfusion (I/R) injury. Methods: Rats were subjected to 1h of 70% hepatic ischaemia, followed by reperfusion or sham. At the end of ischaemia, vehicle (phosphate-buffered saline solution), N-nitro-l-arginine methyl ester (l-NAME) and AM with or without l-NAME were infused via the portal vein. Analysis was performed at pre-ischaemia, ischaemia onset and 1, 2 and 4h after reperfusion. Hepatic tissue blood flow (HTBF) was evaluated by laser Doppler. Results: Plasma AM levels in the I/R groups were significantly lower than the levels in the sham group. AM treatment significantly reduced levels of aspartate transaminase and tissue arginase (P < 0.05). Significant decreases of tumour necrosis factor-?, interleukin-1ß and endothelin-1 levels were also found in the serum. Endothelin-1, malondialdehyde and necrosis were observed more frequently in liver tissue in the AM group than the control (P < 0.05). Tissue nitric oxide, energy charge and HTBF were significantly increased in AM treatment experiments (P < 0.05). Conclusion: The improved HTBF, energy charge and nitric oxide and the reduction of hepatic necrosis, oxidative stress, liver enzymes, endotelin-1 and pro-inflammatory cytokines demonstrate that treatment with AM attenuates liver I/R injury. © Journal compilation © 2008 Blackwell Munksgaard