Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney

1 Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigat ed whether these drugs can prefect against hypoxic damage in a whole kidney preparation. 2 Tolbutamide (200 mu M) and glibenclamide (10 mu M) were applied to the is olated perfused rat kidney prior to changing the gassing from oxygen to nit rogen for 30 min. 3 Hypoxic perfusions resulted in an increased fractional excretion of gluco se (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6 for normoxi c perfusions, mean+/-s.e.mean, P<0.05), which could be completely restored by 200 mu M tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for untrea ted hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total am ount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs 1220+/-1 60 mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtai ned with glibenclamide (10 mu M). 4 In agreement with the effect on functional parameters, ultrastructural an alysis of proximal tubules showed increased brush border preservation in to lbutamide treated kidneys compared to untreated hypoxic kidneys. 5 We conclude that glibenclamide and tolbutamide are both able to reduce hy poxic damage to proximal tubules in the isolated perfused rat kidney when a pplied in the appropriate concentrations.