Age-related changes in homeostasis on inorganic sulfate in male F-344 rats

Abstract

Advanced age in associated with a decline in renal function including decreased glomerular filtration rate, renal blood flow and renal tubular secretion. Endogenous inorganic sulfate homeostasis is maintained by concentration-dependent active renal reabsorption in the proximal tubule. The purpose of this study was to determine the effects of advanced age on: (1) the renal mechanisms for conserving endogenous inorganic organic sulfate and (2) the turnover of inorganic sulfate. Awake, male Fischer 344 rats age 4–5 months and 22–23 months received i.v. acetaminophen, 300 mg/kg, followed 2 h later by i.v. sodium sulfate, 2 mmol/kg, to lower and raise, respectively, plasma inorganic sulfate in order to measure the renal clearance of this anion from plasma at sub- and supraphysiologic concentration ranges. Another group of old and young male F-344 rats received a tracer injection of [ 35S]sodium sulfate to determine the effect of aging on the turnover of the endogenous inorganic sulfate pool. There was no statistically significant effect of advanced age on baseline plasma sulfate concentration or on the renal clearance of inorganic sulfate from plasma. The baseline excretion rate of inorganic sulfate in the senescent animals (0.38 ± 0.25 μmol/min/kg, mean ± S.D., n = 7) was significantly ( P < 0.05) lower than that observed in the young animals (0.64 ± 0.19 μmol/min/kg, n = 8). There was no difference in the turnouver rate constant, as measured by the change in specific activity of urinary [ 35S]sodium sulfate, for the endogenous sulfate pool in old and young animals. Following acetaminophen administration, plasma sulfate concentrations declined similarly in young and old animals. Under the conditions of relative inorganic sulfate depletion, the renal excretion rate of inorganic sulfate decreased to zero in 7 of 8 young rats, whereas the old animals continued to excrete sulfate anion at an average rate of 23% of the baseline value. Aged animals have a defect in active tubular renal reabsorption of sulfate under conditions of sulfate depletion. Age-related changes in the total sulfate excretion rate may reflect changes in the metabolic fate of endogenous sulfate rather than changes in the endogenous production rate of this anion.