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Abstract: TH-PO499

Renal H+/K+ ATPases Mediate Benzamil-Inhibited Urinary H+ Excretion

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic


  • Ayasse, Niklas, Aarhus University, Aarhus, Denmark
  • Lynch, I. Jeanette, University of Florida, Gainesville, Florida, United States
  • Wingo, Charles S., University of Florida, Gainesville, Florida, United States
  • Leipziger, Jens G., Aarhus University, Aarhus, Denmark

Acute inhibition of ENaC causes a marked urinary alkalization. It was previously assumed that the so-called “voltage hypothesis” explains this urinary pH effect. The “voltage hypothesis” states that the lumen-negative ENaC-dependent transepithelial voltage provides the driving force for H+ secretion via the vacuolar H+ ATPase in neighbouring α-intercalated cells of the CD. In two preceding studies, we have contested the “voltage hypothesis”. This, therefore, calls for an alternative explanation of the mechanism of ENaC blocker-mediated urinary alkalisation. Here we present data that strongly supports the involvement of renal H+/K+ ATPases, which are also located in the apical membrane of the α-IC.


In vivo studies in anesthetized mice were conducted to continuously measure urine output, urine electrolytes and urine pH.


Application of benzamil acutely alkalized the urine (delta pH: 0.33±0.07). In parallel, the ambient luminal [K+] dropped markedly. In animals fed a low K+ diet, the benzamil-induced urinary alkalisation was greatly enhanced (delta pH: 0.74±0.12) and a significantly lower urine [K+] nadir was reached. In double knock out mice lack both isoforms of the H+/K+ ATPases the benzamil effect was completely absent.


These data support the following explanation. ENaC inhibitors elicit their effect indirectly via their marked K+ sparing property. They induced a strong drop of the ambient luminal [K+] concentration with impedes H+/K+ ATPases function and thus tubular H+ secretion. Thus, we postulate that the lack of substrate (K+) causes the luminal alkalisation by benzamil.


  • Government Support - Non-U.S.