Contrast media induced changes in tubular electrophysiology and glomerular filtration rate in the mouse kidney

The isolated perfused mouse proximal tubule was used to examine electrophysiologic effects of diatrizoate and ioversol. Luminal or basolateral application of diatrizoate resulted in a dose-dependent, reversible hyperpolarization of the proximal tubule cell basolateral membrane potential (V-B), which could be abolished by the addition of 10 mu M probenecid. While there was a modest reduction in intracellular ATP following a 60-min exposure to diatrizoate, there was no deterioration of V-B after 90 min of diatrizoate exposure, even following a 20-min hypoxic insult. Ioversol did not elicit an electrical response. Neither diatrizoate nor ioversol significantly affected transepithelial potential (V-T) in the isolated perfused medullary thick ascending limb. In vivo studies showed that only the ionic contrast agent diatrizoate significantly reduced glomerular filtration rate, by 70%. The observed acute contrast media induced reduction in glomerular filtration rate does not appear to depend on direct renal tubular cytotoxicity.