Background
Liver function is affected during ischemia/reperfusion (IR). We evaluated the effect of the aging process on selected parameters determining the NO level in rat liver subjected to IR.
Methods
The animals were divided into the C-2 and the IR-2 group of young rats (2-4 months old) and the C-12 and the IR-12 group of older rats (12-14 months old). Livers belonging to the IR-2 and the IR-12 group were subjected to partial ischemia (60 min) and reperfusion (4 h). Blood samples were obtained after surgeries to estimate the activity of aminotransferases, as well as just before ischemia and during reperfusion (15, 120, and 240 min) to estimate concentration of arginine (Arg) and its derivatives: asymmetric and symmetric dimethylarginine (ADMA, SDMA). After IR, dimethylarginine dimethylaminohydrolase (DDAH) activity and protein concentration of inducible nitric oxide synthase (iNOS) were measured in liver homogenates.
Results
In the IR-2 group ADMA level increased the most between 15 and 120 min of reperfusion and was the highest of all the groups (0.72 卤 0.2 渭mol/l). In the IR-12 group ADMA level decreased significantly and was lower compared to all the other groups at 15 min (0.42 卤 0.2 渭mol/l) and to IR-2 at 120 (0.52 卤 0.1 渭mol/l) and 240 min (0.38 卤 0.1 渭mol/l) of reperfusion. Only the IR-2 group SDMA level increased significantly between 15 (0.75 卤 0.9 渭mol/l) and 240 min (1.0 卤 1.2 渭mol/l) of reperfusion. At the beginning of the surgery the Arg level was significantly higher in young rats (C-2: 102.1 卤 35.7 渭mol/l; IR-2: 114.63 卤 28.9 渭mol/l) than in older ones (C-12: 41.88 卤 44.7 渭mol/l; IR-12: 28.64 卤 30.6 渭mol/l). In the C-2 group the Arg level (77.41 卤 37.5 渭mol/l) and Arg/ADMA (A/A) ratio (138.03 卤 62.8 渭mol/l) were significantly higher compared to the ischemic groups at 15 min and to all the other groups at 120 (Arg: 47.17 卤 31.7 渭mol/l; A/A: 88.28 卤 66.2 渭mol/l) and 240 min (Arg: 43.87 卤 21.9 渭mol/l; A/A: 118.02 卤 106.3 渭mol/l). In the IR-2 group Arg level (11.4 卤 12.0 渭mol/l) and A/A ratio (16.11 卤 16.2 渭mol/l) decreased significantly at 15 min and during the next phase of reperfusion the levels of those parameters were low, comparably to those in IR-12. As a result of IR, a decrease in DDAH activity and an increase in iNOS protein concentration were observed only in the young rats.
Conclusions
We found that in the non-ischemic groups the Arg level may be affected by the aging process. Under IR conditions, important changes in DDAH-ADMA-NO pathway were observed only in young livers.
