Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet

Bangchen Wang, Donghai Wen, Huaqing Li, Jun Wang-France, Steven C. Sansom

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance. We used free-flow micropuncture to measure the [K+] in the early distal tubule (EDT [K+]) before and after furosemide treatment. Furosemide increased the EDT [K+] in WT on CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K+] of KO on LNaHK or WT on HK. Furosemide-sensitive Na+ excretion was significantly greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split-open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but similar density in mice on LNaHK, compared with CTRL. No difference was found in the density or Po of the 30 pS K channels between the two groups. These results indicate mice on LNaHK exhibited furosemide-sensitive net K+ secretion in the TAL that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude that furosemide is a K-sparing diuretic by decreasing the TAL net K+ secretion in subjects on LNaHK.

Original languageEnglish (US)
Pages (from-to)864-875
Number of pages12
JournalKidney International
Volume92
Issue number4
DOIs
StatePublished - Oct 2017

Fingerprint

Extremities
Diet
Furosemide
Diuretics
Kidney
Knockout Mice
Punctures
Drinking Water

Keywords

  • K secretion
  • NKCC2
  • ROMK
  • furosemide
  • thick ascending limb

ASJC Scopus subject areas

  • Nephrology

Cite this

Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet. / Wang, Bangchen; Wen, Donghai; Li, Huaqing; Wang-France, Jun; Sansom, Steven C.

In: Kidney International, Vol. 92, No. 4, 10.2017, p. 864-875.

Research output: Contribution to journalArticle

Wang, Bangchen ; Wen, Donghai ; Li, Huaqing ; Wang-France, Jun ; Sansom, Steven C. / Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet. In: Kidney International. 2017 ; Vol. 92, No. 4. pp. 864-875.
@article{da4b48b994024ec5910dbea7186a1901,
title = "Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet",
abstract = "Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance. We used free-flow micropuncture to measure the [K+] in the early distal tubule (EDT [K+]) before and after furosemide treatment. Furosemide increased the EDT [K+] in WT on CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K+] of KO on LNaHK or WT on HK. Furosemide-sensitive Na+ excretion was significantly greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split-open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but similar density in mice on LNaHK, compared with CTRL. No difference was found in the density or Po of the 30 pS K channels between the two groups. These results indicate mice on LNaHK exhibited furosemide-sensitive net K+ secretion in the TAL that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude that furosemide is a K-sparing diuretic by decreasing the TAL net K+ secretion in subjects on LNaHK.",
keywords = "K secretion, NKCC2, ROMK, furosemide, thick ascending limb",
author = "Bangchen Wang and Donghai Wen and Huaqing Li and Jun Wang-France and Sansom, {Steven C.}",
year = "2017",
month = "10",
doi = "10.1016/j.kint.2017.04.009",
language = "English (US)",
volume = "92",
pages = "864--875",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Net K+ secretion in the thick ascending limb of mice on a low-Na, high-K diet

AU - Wang, Bangchen

AU - Wen, Donghai

AU - Li, Huaqing

AU - Wang-France, Jun

AU - Sansom, Steven C.

PY - 2017/10

Y1 - 2017/10

N2 - Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance. We used free-flow micropuncture to measure the [K+] in the early distal tubule (EDT [K+]) before and after furosemide treatment. Furosemide increased the EDT [K+] in WT on CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K+] of KO on LNaHK or WT on HK. Furosemide-sensitive Na+ excretion was significantly greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split-open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but similar density in mice on LNaHK, compared with CTRL. No difference was found in the density or Po of the 30 pS K channels between the two groups. These results indicate mice on LNaHK exhibited furosemide-sensitive net K+ secretion in the TAL that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude that furosemide is a K-sparing diuretic by decreasing the TAL net K+ secretion in subjects on LNaHK.

AB - Because of its cardio-protective effects, a low-Na, high-K diet (LNaHK) is often warranted in conjunction with diuretics to treat hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. Wild-type (WT) or Renal Outer Medullary K channel (ROMK) knockout mice (KO) were given a regular (CTRL), LNaHK, or high-K diet (HK) for 4-7 days. On LNaHK, mice treated with either IP furosemide for 12 hrs, or given furosemide in drinking water for 7 days, exhibited decreased K clearance. We used free-flow micropuncture to measure the [K+] in the early distal tubule (EDT [K+]) before and after furosemide treatment. Furosemide increased the EDT [K+] in WT on CTRL but decreased that in WT on LNaHK. Furosemide did not affect the EDT [K+] of KO on LNaHK or WT on HK. Furosemide-sensitive Na+ excretion was significantly greater in mice on LNaHK than those on CTRL or HK. Patch clamp analysis of split-open TALs revealed that 70-pS ROMK exhibited a higher open probability (Po) but similar density in mice on LNaHK, compared with CTRL. No difference was found in the density or Po of the 30 pS K channels between the two groups. These results indicate mice on LNaHK exhibited furosemide-sensitive net K+ secretion in the TAL that is dependent on increased NKCC2 activity and mediated by ROMK. We conclude that furosemide is a K-sparing diuretic by decreasing the TAL net K+ secretion in subjects on LNaHK.

KW - K secretion

KW - NKCC2

KW - ROMK

KW - furosemide

KW - thick ascending limb

UR - http://www.scopus.com/inward/record.url?scp=85021846772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021846772&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2017.04.009

DO - 10.1016/j.kint.2017.04.009

M3 - Article

C2 - 28688582

AN - SCOPUS:85021846772

VL - 92

SP - 864

EP - 875

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -