Isolated perfused rat kidney as a tool in the investigation of renal handling and effects of nonsteroidal antiinflammatory drugs

Abstract

An isolated perfused rat kidney (IPK) preparation is described in which renal perfusion flow, perfusion pressure, urinary flow, urinary pH, and glomerular filtration rate (GFR) are recorded continuously during the perfusion experiment. The usefulness of this IPK system in studying the renal handling and the effects of non-steroidal antiinflammatory drugs (NSAIDs) is shown using salicyluric acid (SU), salicylic acid (SA), and naproxen (NA). Excretion of SU involves glomerular filtration, active secretion, and passive reabsorption. The excretion rates of SA and NA were both much lower than their filtration rate, indicating extensive reabsorption. All three drugs accumulate in the 1PK but at different levels. SU accumulates much more than either SA or NA. The effects on renal function were different for the three drugs studied. SU had no effect on kidney function. SA perfusate concentrations greater than 100 $\text{μg}\text{mL}$ caused diuresis and natriuresis, while SA concentrations less than 100 $\text{μg}\text{mL}$ did not influence kidney function. NA perfusate concentrations ranging from 0.16 to 25 $\text{μg}\text{mL}$ caused a decrease in urinary flow and sodium excretion. Very high NA concentrations (⪢500 $\text{μg}\text{mL}$) caused an increase in urinary flow and sodium excretion. We conclude that the IPK is a suitable preparation for characterizing and comparing renal handling and effects of NSAIDs.