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Abstract: TH-OR26

Dietary Anion Prioritizes Pendrin Activation over Aldosterone

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Tahaei, Seyedmohammadebrahim, Johns Hopkins Medicine, Baltimore, Maryland, United States
  • Wall, Susan M., Emory University School of Medicine, Atlanta, Georgia, United States
  • Welling, Paul A., Johns Hopkins Medicine, Baltimore, Maryland, United States
Background

It is well established that the bicarbonate-chloride exchanger, Pendrin, is physiologically modulated in intercalated cells to maintain acid-base balance. Because Pendrin is also upregulated by aldosterone and angiotensin II to preserve intravascular fluid volume but is inhibited in high aldosterone states of dietary potassium-chloride loading, it has been suggested pendrin may be differentially regulated to help sculpt the distinct adaptive responses of aldosterone to volume contraction and hyperkalemia. Here, we challenge this hypothesis by investigating how Pendrin is modulated by dietary potassium salts.

Methods

C57/Bl6J male mice (2 month old) were randomized to matched control (2% KCl), high potassium bicarbonate (13.4% KHCO3), or high potassium chloride (10% KCl) diets (4 days). A separate cohort of mice was randomized to a switch anion diet protocol, whereby mice were first adapted to the high KHCO3 or the high KCl diet (4 days), and the response to changing the anion in the context of high potassium, high aldosterone was assessed at 24 and 48 hours. Aldosterone and plasma electrolytes were measured by standard methods. Kidney Pendrin mRNA and protein abundance were assessed by qRT-PCR and western blot, respectively.

Results

Dietary KCl and KHCO3 loading increased plasma potassium and aldosterone to the same extent but had opposite effects on pendrin abundance. KHCO3 loading increased pendrin, while dietary KCl loading inhibited it. Pendrin protein and transcript abundance decreased within 24 hours of switching the high KHCO3 diet to high KCl, and the response was coincident with an increase in plasma chloride and a decrease in bicarbonate. Switching the high KCl diet to high KHCO3 had the opposite response, increasing pendrin protein and transcript as plasma bicarbonate increased and chloride decreased. Neither anion switch protocol changed the extent of hyperaldosterone or hyperkalemia.

Conclusion

Pendrin regulation is prioritized by the dietary anion. Ingestion of an alkaline-rich, high potassium diet drives pendrin expression to prevent metabolic alkalosis, while pendrin is rapidly downregulated to limit hyperchloremic acidosis with consumption of a high KCl diet. We conclude pendrin is differently regulated depending on the potassium salt to control acid-base balance rather than to maintain K+ homeostasis.

Funding

  • NIDDK Support