ACUTE EFFECTS OF GENTAMICIN ON THICK ASCENDING LIMB FUNCTION IN THE RAT

It is well established that the aminoglycoside antibiotics can adverse ly affect proximal tubule function. Predominantly indirect evidence su ggests that aminoglycosides may also affect function of more distal ne phron segments. The present study utilized whole kidney clearance, in vivo micropuncture and in vitro microperfusion to directly determine w hether acute gentamicin treatment affects sodium chloride transport in the thick ascending limb of the loop of Henle. Gentamicin (25 mg/kg) significantly increased urine flow, as well as sodium, potassium and c hloride excretion within 15 min of intravenous injection. Glomerular f iltration rate and proximal tubule fluid reabsorption were not altered by acute gentamicin treatment. In contrast, both fractional and absol ute loop chloride transport was significantly decreased. In the in vit ro microperfused medullary thick ascending limb, luminal but not basol ateral administration of gentamicin (1 mM) significantly decreased chl oride reabsorption when compared to time controls. These data suggest that the increased urine and electrolyte excretion associated with acu te gentamicin treatment is, at least in part, a consequence of decreas ed transport in the thick ascending limb of Henle's loop.