IntroductionPreviously we demonstrated in rats that chronic hyperkalemia had no effect on ammonium secretion by the proximal tubule in vivo but that high K+ concentrations inhibited ammonium absorption by the medullary thick ascending limb in vitro. These observations suggested that chronic hyperkalemia may reduce urinary ammonium excretion through effects on medullary transport events. To examine directly the effects of chronic hyperkalemia on medullary ammonium accumulation and collecting duct ammonium secretion, micropuncture experiments were performed in the inner medulla of Munich-Wistar rats pair fed a control or high-K+ diet for 7-13 d. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations for base and tip collecting duct and vasa recta. Chronic K+ loading was associated with significant systemic metabolic acidosis and a 40% decrease in urinary ammonium excretion. In control rats, 15% of excreted ammonium was secreted between base and tip collecting duct sites. In contrast, no net transport of ammonium was detected along the collecting duct in high-K+ rats. The decrease in collecting duct ammonium secretion in hyperkalemia was associated with a decrease in the NH3 concentration difference between vasa recta and collecting duct. Changes in systemic potassium balance have an important influence on urinary net acid excretion, predominantly through effects on urinary ammonium excretion ( 1-3).' Potassium retention and clinical hyperkalemia are associated with a decrease in urinary ammonium excretion that is thought to contribute to the metabolic acidosis that accompanies a variety of pathologic conditions, such as mineralocorticoid deficiency and chronic renal insufficiency (2-8). Based on the observations that an increase in extracellular potassium concentration decreased ammonium synthesis by renal cortical slices, renal cortical tubule suspensions, and isolated, perfused proximal tubules (9-1 1 ), it had generally been assumed that the decrease in urinary ammonium excretion with hyperkalemia was the result ofa decrease in ammonium production and secretion by the proximal tubule. Recently, however, we have shown that dietary K+ loading sufficient to cause chronic hyperkalemia in rats markedly reduced renal ammonium production and urinary ammonium excretion, with no significant effect on either net ammonium secretion by or ammonium delivery out ofthe proximal convoluted tubule (12). These findings suggested that-the decrease in ammonium excretion in hyperkalemia may be the result of an impaired ability to transfer the ammonium secreted by the proximal tubules to the final urine.A possible mechanism by which hyperkalemia could impair transfer of ammonium to the urine was identified in studies of isolated, perfused medullary thick ascending limbs from rats. Active absorption of NH 4+ by the medullary thick ascending limb plays an important role in transferring the ammonium produced by proximal tubules from loops of Henle to collecting ducts in the renal medulla (13,...