Iodinated contrast media (CM) have adverse effects which may result in contrast induced acute kidney injury. Oxidative stress is believed to play a role in CM induced kidney injury. We test the hypothesis that oxidative stress and reduced nitric oxide in tubules are consequences of CM-induced direct cell damage, and that increased local oxidative stress may increase tubulo-glomerular feedback. Rat thick ascending limbs (TAL) were isolated and perfused. Superoxide and nitric oxide were quantified using fluorescence techniques. Cell death rate was estimated using propidium iodide and trypan blue. The function of macula densa and tubulo-glomerular feedback responsiveness were measured in isolated perfused juxta-glomerular apparatuses (JGA) of rabbits. The expression of genes related to oxidative stress and the activity of superoxide dismutase (SOD) were investigated in the renal medulla of rats which received CM. CM increased superoxide concentration and reduced NO bioavailability in TAL. Propidium iodide fluorescence and trypan blue uptake increased more in CM perfused TAL than in controls, indicating increased rate of cell death. There were no marked acute changes in the expression of genes related to oxidative stress in medullary segments of Henle's loop. SOD activity did not differ between CM and control groups. The tubulo-glomerular feedback in isolated JGA was increased by CM. Tubular cell damage and accompanying oxidative stress in our model are consequences of CM-induced direct cell damage, which also modifies the tubulo-vascular interaction at the macula densa, and may therefore contribute to disturbances of renal perfusion and filtration.