Potassium-sparing effects of furosemide in mice on high-potassium diets

Bangchen Wang, Steven C. Sansom

Research output: Contribution to journalReview article

Abstract

In individuals on a regular “Western” diet, furosemide induces a kaliuresis and reduction in plasma K concentration by inhibiting Na reabsorption in the thick ascending limb of Henle’s loop, enhancing delivery of Na to the aldosterone-sensitive distal nephron. In the aldosterone-sensitive distal nephron, the increased Na delivery stimulates K wasting due to an exaggerated exchange of epithelial Na channel-mediated Na reabsorption of secreted K. The effects of furosemide are different in mice fed a high-K, alkaline (HK) diet: the large-conductance Ca-activated K (BK) channel, in conjunction with the BK β4-subunit (BK-α/β4), mediates K secretion from intercalated cells (IC) of the connecting tubule and collecting ducts. The urinary alkaline load is necessary for BK-α/β4-mediated K secretion in HK diet-fed mice. However, furosemide acidifies the urine by increasing vacuolar ATPase expression and acid secretion from IC, thereby inhibiting BK-α/β4-mediated K secretion and sparing K. In mice fed a low-Na, high-K (LNaHK) diet, furosemide causes a greater increase in plasma K concentration and reduction in K excretion than in HK diet-fed mice. Micropuncture of the early distal tubule of mice fed a LNaHK diet, but not a regular or a HK diet, reveals K secretion in the thick ascending limb of Henle’s loop. The sites of action of K secretion in individuals consuming a high-K diet should be taken into account when diuretic agents known to waste K with low or moderate K intakes are prescribed.

Original languageEnglish (US)
Pages (from-to)F970-F973
JournalAmerican Journal of Physiology - Renal Physiology
Volume316
Issue number5
DOIs
StatePublished - May 2019

Keywords

  • BK
  • Furosemide
  • High-K diet
  • ROMK

ASJC Scopus subject areas

  • Physiology
  • Urology

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