Protection from renal ischemia reperfusion injury by an endothelin a-receptor antagonist BQ-123 in relation to nitric oxide production

7- SUMMARY Protection From Renal Ischemia Reperfusion Injury By An Endothelin A-Receptor Antagonist BQ-123 In Relation To Nitric Oxide Production The aim of this study was to investigate whether the protective effect of ETA receptor antagonist BQ-123 (BQ) against renal I/R injury is related to nitric oxide (NO) production by combining it with L-Arginine (L-Arg) or the NO synthase inhibitor L-NAME through hemodynami, plasma BUN, creatinine (Cr) and Na concentration and renal oxidant/antioxidant system. Male Sprague Dawley rats were divided into 6 groups each has 8 rats; control, I/R, L-NAME and BQ+L-NAME groups Control, I/R, L-NAME, BQ, BQ+L- NAME, BQ+L-NAME+L-Arg. 30 min renal ischemia and 2 hours reperfusion were performed in all groups except Control group. The activity of CAT was found increased in BQ group in comparison with Control, I/R, L-NAME and BQ+L-NAME groups (p<0.05) and decreased in L- NAME groups in comparison with the other groups (p<0.05), except I/R group. The SOD activity of BQ group was higher than all other groups (p<0.05), except BQ+L-NAME+L-Arg group. The GSH-Px activity was lower in control group than the other groups (p<0.05), except BQ+L-NAME group and lower in BQ+L-NAME group than BQ+L-NAME+L-Arg group (p<0.01). The activity of XO was higher in I/R group than all the other groups (p<0.05), higher in L- NAME and BQ than Control group (p<0.05). The level of tissue TBARS were increased in I/R and L-NAME groups in comparison with the other groups (p<0.05). The MPO activities of Control and BQ groups were signicantly lower than the other groups (p<0.05). The PC content of control group was lower than all the other groups (p<0.001), as well the PC contents of I/R and L- NAME groups were higher than BQ and BQ+L-NAME+L-Arg groups (p<0.05). The tissue NO levels of I/R, BQ ve BQ+L-NAME+L-Arg groups were significantly higher than Control, L-NAME and BQ+L-NAME groups (p<0.05). The plasma BUN was increased in BQ+L-NAME+L-Arg group in comparison with the other groups (p<0.05), except L-NAME, and as well significantly increased in I/R and L-NAME groups in comparison with BQ groups (p<0.05). The plasma Cr was lower in BQ+L-NAME+L-Arg groups than I/R and L-NAME groups (p<0.05). The plasma Na concentration was lower in BQ group than the all other groups (p<0.05) and in addition higher in L-NAME group than BQ+L- NAME+L-Arg group (p<0.05). Blood pressures during reperfusion period in L- NAME, BQ+L-NAME ve BQ+L-NAME+L-Arg groups were higher than during preischemia and ischemia periods (p<0.05), however blood pressures at 60th 74and 120th min of reperfusion in Control and BQ groups were lower than during ischemia period (p<0.05). Blood pressures of L-NAME, BQ+L-NAME and BQ+L- NAME+L-Arg groups were significantly higher than the other groups during reperfusion period (p<0.05). It can be concluded that ETA receptor antagonist BQ-123 may be revealed a protective agent against renal I/R injury with a possible secondary pathway via its antioxidant effects. In addition, the present findings are abolished by a NOS blocker and a restoration by addition of the NO precursor L-Arg, suggested that are mediated via a NO-dependent mechanism. 75