Influence of NSAID-Induced Inhibition of Renal Prostaglandin Synthesis on Inorganic Sulfate Clearance in Rats

Abstract

Abstract

The objective of the present investigation was to examine the influence of inhibition of renal prostaglandin synthesis on the renal clearance of inorganic sulfate, an electrolyte involved in the biotransformation of both exogenous and endogenous substrates. Homeostasis of inorganic sulfate is maintained predominantly by renal reabsorption in the proximal tubule. Using a crossover study design, the renal clearance of sulfate was assessed in conscious female Lewis rats during control periods and following the infusion of two structurally dissimilar nonsteroidal anti-inflammatory drugs, ibuprofen (IBU) and indomethacin (INDO). Animals were infused with IBU or INDO to achieve steady state concentrations of 59 ± 8 μg/ml (mean ± SD) of IBU and 22 ± 3 μg/ml of INDO. At these serum concentrations, IBU and INDO produced >80% decrease in the urinary excretion of prostaglandin (PG) E₂. Treatment with either IBU or INDO significantly increased the renal clearance of sulfate, but did not alter the glomerular filtration rate as assessed by creatinine clearance. The role of prostaglandins in the effects of IBU and INDO on sulfate homeostasis was investigated by examining the influence of concomitant intraarterial PGE₂ administration (infusion of 0.1 μg/min) on nonsteroidal anti-inflammatory drug-induced alterations in sulfate renal clearance. Although PGE₂ alone did not significantly alter the renal clearance of inorganic sulfate or that of creatinine, the PGE₂ infusion abolished the effects of IBU on sulfate renal clearance. Concomitant PGE₂ administration also significantly increased the sulfate reabsorption rate in INDO-treated animals; other parameters were not significantly changed, although the fractional reabsorption of sulfate tended to increase (P = 0.17). The reason for the less pronounced effect on PGE₂ on the INDO-sulfate interaction is as yet unknown, but may be partly due to additional mechanisms involved in the INDO-induced alterations in sulfate clearance.