Effects of Amifostine on Glycerol‐Pretreated Rabbit Kidneys

: Glycerol‐induced acute renal failure is an experimental model for myoglobinuric nephropathy. Amifostine is a cytoprotective agent which scavenges the free radicals. Since there is enhanced production of reactive oxygen metabolites in glycerol‐induced acute renal failure, we wanted to examine whether amifostine has a protective role against vascular reactivity and histological changes in kidneys isolated from glycerol‐pretreated rabbits. Perfusion pressure was recorded from kidneys obtained from rabbits injected with glycerol 3 hr before the experiments and from glycerol‐pretreated and non‐pretreated rabbits injected with amifostine 30 min. before the experiments. Acetylcholine‐induced (10−8‐10−5 M) vasodilatation was tested following the construction of submaximal vasoconstriction by phenylephrine. Histological investigation was performed using light microscope. Acetylcholine‐induced vasodilatation was found to be significantly decreased in glycerol, glycerol+amifostine and amifostine groups compared to controls at all concentrations. Reduction in acetylcholine‐induced vasodilation was more prominent in amifostine group compared to amifostine+glycerol group. There was histological renal damage in all experimental groups and this damage was more pronounced in glycerol+amifostine group. In conclusion, contrary to expectation, amifostine per se led to histological damage and potentiated the histological damage caused by glycerol and produced a decrease in acetylcholine‐induced vasodilatation. The mechanisms by which amifostine exerts its effects are not known.