DuBose T D, Good D W
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
J Clin Invest. 1992 Oct;90(4):1443-9. doi: 10.1172/JCI116011.
Previously 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. The fall in the NH3 concentration difference across the collecting duct in high-K+ rats was due entirely to a decrease in [NH3] in the medullary interstitial fluid, with no change in [NH3] in the collecting duct. These results indicate that impaired accumulation of ammonium in the medullary interstitium, secondary to inhibition of ammonium absorption in the medullary thick ascending limb, may play an important role in reducing collecting duct ammonium secretion and urinary ammonium excretion during chronic hyperkalemia.
此前我们在大鼠中证明，慢性高钾血症对体内近端小管的铵分泌没有影响，但高钾浓度在体外会抑制髓袢升支粗段的铵吸收。这些观察结果表明，慢性高钾血症可能通过影响髓质转运过程来减少尿铵排泄。为了直接研究慢性高钾血症对髓质铵积累和集合管铵分泌的影响，我们对成对饲养的慕尼黑-威斯塔大鼠进行了微穿刺实验，这些大鼠分别喂食对照饮食或高钾饮食7 - 13天。测量原位pH值和总氨浓度，以计算集合管基部和尖端以及直小血管的氨浓度。慢性钾负荷与显著的全身性代谢性酸中毒以及尿铵排泄减少40%相关。在对照大鼠中，15%的排泄铵是在集合管基部和尖端之间分泌的。相比之下，在高钾大鼠的集合管中未检测到铵的净转运。高钾血症时集合管铵分泌的减少与直小血管和集合管之间氨浓度差的降低有关。高钾大鼠集合管氨浓度差的下降完全是由于髓质间质液中[NH₃]的降低，而集合管中[NH₃]没有变化。这些结果表明，继发于髓袢升支粗段铵吸收受抑制的髓质间质中铵积累受损，可能在慢性高钾血症期间减少集合管铵分泌和尿铵排泄中起重要作用。
