1 The renal handling and effects of S( +)-and R(-)-ibuprofen have been studied in the isolated perfused kidpney (IPK) of the rat. 2 Both ibuprofen enantiomers were extensively reabsorbed and accumulated in the kidney in a concentration-dependent manner. No pharmacokinetic differences were observed between the two enantiomers.3 S(+)-ibuprofen concentrations ranging from 0.25 to 25 pgml-1 (1.2 to 120pM) caused a decrease in urinary flow, glomerular filtration rate (GFR) and electrolyte excretion. Urinary pH and excretion of glucose were not influenced. R(-)-ibuprofen concentrations ranging from 2.5 to 25g ml-1 (12 to 120pUM) also decreased urinary flow and electrolyte excretion. This decrease, however, was less than observed with S( + )-ibuprofen. GFR, urinary pH and glucose excretion were not affected by' R(-)-ibuprofen. Prostaglandin E2 (PGE2) concentrations of 133 ng ml-1 reversed the effects on renal function of both enantiomers.4 Very high S(+ )-and R(-)-ibuprofen concentrations (>400,pg ml-) resulted in an increase in urinary flow and fractional excretion of sodium, chloride, potassium, glucose and calcium. 5 It is concluded that the pharmacokinetic behaviour of ibuprofen in the kidney is not stereoselective. Relatively high concentrations of both enantiomers increased the urinary flow and electrolyte excretion in a nonstereoselective manner. Lower concentrations of S( + -ibuprofen decreased urinary flow and electrolyte excretion. The pharmacologically inactive R(-)-ibuprofen was also able to affect renal function in a similar way, but at different concentrations. These effects on renal function are probably caused by inhibition of PGE2 synthesis.

Glomerular hemodynamics were studied of isolated perfused kidneys of 12-wk-old normotensive (NR) and spontaneously hypertensive (SHR) rats, using Pluronic F108 (BASF, Wyandotte, MI, USA) as a plasma expander. Glomerular filtration rate (GFR), proximal tubular hydrostatic pressure (PT) and glomerular capillary hydrostatic pressure (PGC) were approximately linearly related with renal perfusion pressure. PGC measured directly by micropuncture was comparable to PGC calculated from other parameters of glomerular dynamics using pore theory. We conclude that GFR in isolated kidneys perfused with Pluronic F108 is lower than in vivo, mainly as a result of an increase in PT. This rise in tubular pressure is due to an increased urine flow rate and an elevated tubular fluid viscosity. The difference in glomerular dynamics between NR and SHR kidneys is the result of an increased preglomerular vascular resistance in SHR, possibly due to an adaptive hypertrophic reaction to a sustained hypertension.

Chloride movement across the wall of the rabbit submaxillary duct has been studied. It was shown that the chloride diffusion from blood to luminal side was determined primarily by the existing transmucosal potential difference. From the fact that the ouabain-poisoned duct showed symmetrical behavior with respect to the chloride diffusion potentials in both directions and the fact that the measured chloride flux behaved as predicted according to the Goldman equation, it was suggested that a single barrier, rather than a series membrane system, determined the chloride movement. The permeability coefficients for chloride, in the order of 5.5 x 10(-5) cm sce-1 are much larger than would be expected for cell membranes. These findings in combination with the observations that mannitol permeability is higher during chloride perfusion than during sulfate perfusion and the observed electron-microscopic changes favor the concept of the existence of an extracellular route in chloride diffusion. An equivalent electrical circuit is given in order to evaluate the contribution of the chloride shunt more quantitatively. Calculations showed that the ductal resistivity during sulfate perfusion has a value in the order of 434 omega cm2, while during chloride perfusion this value is lowered to 48 omega cm2, indicating that the ductal wall can change from a tight to a leaky epithelium. The implications of these findings are discussed.

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The renal handling of salicylic acid (SA) and its effects on renal function were studied in the isolated perfused rat kidney (IPK). The renal handling of SA is dominated by reabsorption and only a small fraction of the filtered SA is excreted into the urine. Reabsorption is a passive process and is dependent on urinary pH. Because of the extensive reabsorption, no decrease in perfusate concentration can be observed in the course of the IPK experiment. SA accumulated slightly in the IPK and this accumulation is concentration dependent. Small amounts of SA were converted to salicyluric acid (SU), the glycine conjugate of SA. SA concentrations higher than 100 micrograms/ml caused an immediate increase in urinary flow and in fractional excretion of sodium, potassium, chloride and calcium. Fractional excretion of glucose increased gradually. Glomerular filtration rate, renal perfusion flow, renal pressure and fractional excretion of magnesium were not affected by SA. The effects were dependent on the SA concentration. Although SA is a classical non-steroidal antiinflammatory drug (NSAID), its influence on renal function appears to be different from other NSAIDs which are usually associated with a reduction in urinary flow and salt excretion.