Indometacin: renal handling and effects in the isolated perfused rat kidney

We investigated renal handling and effects of indometacin on renal function in the isolated perfused rat kidney (IPK). Indometacin concentrations less than 2.5 ng/ml did not influence renal function, while higher concentrations caused a decrease in urinary flow and electrolyte excretion. The presence of 133 ng/ml prostaglandin E2 (PGE2) in the perfusate fully opposed these effects on kidney function. Only a small fraction of the filtered indometacin is excreted into the urine, indicating extensive reabsorption of the compound. This is probably a passive process, dependent on the tubular load, urinary pH and urinary flow. Indometacin accumulates extensively in the IPK, causing a kidney to perfusate ratio between 5 and 9. Accumulation decreased with increasing perfusate concentration. This can be explained by active secretion: increasing the perfusate concentration leads to a saturation of the active secretion and a decrease in the relative accumulation. We conclude that indometacin accumulates extensively in the IPK, that it affects kidney function and that this influence is probably caused by the inhibition of PGE2 synthesis.