Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Aldosterone-dependent and -independent regulation of Na+ and K+ excretion and ENaC in mouse kidneys

Aldosterone-dependent and -independent regulation of Na+ and K+ excretion and ENaC in mouse kidneys We investigated the regulation of Na+ and K+ excretion and the epithelial Na+ channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods to assess excretion and electrophysiology and Western blot analysis to test for ENaC activity and processing. After 1 day of dietary Na+ restriction, AS−/− mice lost more Na+ in the urine than AS+/+ mice did. After 1 wk on this diet, both genotypes strongly reduced urinary Na+ excretion, but creatinine clearance decreased only in AS−/− mice. Only AS+/+ animals exhibited increased ENaC function, assessed as amiloride-sensitive whole cell currents in collecting ducts or cleavage of αENaC and γENaC in Western blots. To assess the role of aldosterone in the excretion of a K+ load, animals were fasted overnight and refed with high-K+ or low-K+ diets for 5 h. Both AS+/+ and AS−/− mice excreted a large amount of K+ during this period. In both phenotypes the excretion was benzamil sensitive, indicating increased K+ secretion coupled to ENaC-dependent Na+ reabsorption. However, the increase in plasma K+ under these conditions was much larger in AS−/− animals than in AS+/+ animals. In both groups, cleavage of αENaC and γENaC increased. However, Na+ current measured ex vivo in connecting tubules was enhanced only in AS+/+ mice. We conclude that in the absence of aldosterone, mice can conserve Na+ without ENaC activation but at the expense of diminished glomerular filtration rate. Excretion of a K+ load can be accomplished through aldosterone-independent upregulation of ENaC, but aldosterone is required to excrete the excess K+ without hyperkalemia. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Physiology-Renal Physiology The American Physiological Society

Aldosterone-dependent and -independent regulation of Na+ and K+ excretion and ENaC in mouse kidneys

Download PDF
12 pages

Loading next page...
 
/lp/the-american-physiological-society/aldosterone-dependent-and-independent-regulation-of-na-and-k-excretion-1CfcPNHAbJ

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

ISSN
1931-857x
eISSN
1522-1466
DOI
10.1152/ajprenal.00204.2020
Publisher site
See Article on Publisher Site

Abstract

We investigated the regulation of Na+ and K+ excretion and the epithelial Na+ channel (ENaC) in mice lacking the gene for aldosterone synthase (AS) using clearance methods to assess excretion and electrophysiology and Western blot analysis to test for ENaC activity and processing. After 1 day of dietary Na+ restriction, AS−/− mice lost more Na+ in the urine than AS+/+ mice did. After 1 wk on this diet, both genotypes strongly reduced urinary Na+ excretion, but creatinine clearance decreased only in AS−/− mice. Only AS+/+ animals exhibited increased ENaC function, assessed as amiloride-sensitive whole cell currents in collecting ducts or cleavage of αENaC and γENaC in Western blots. To assess the role of aldosterone in the excretion of a K+ load, animals were fasted overnight and refed with high-K+ or low-K+ diets for 5 h. Both AS+/+ and AS−/− mice excreted a large amount of K+ during this period. In both phenotypes the excretion was benzamil sensitive, indicating increased K+ secretion coupled to ENaC-dependent Na+ reabsorption. However, the increase in plasma K+ under these conditions was much larger in AS−/− animals than in AS+/+ animals. In both groups, cleavage of αENaC and γENaC increased. However, Na+ current measured ex vivo in connecting tubules was enhanced only in AS+/+ mice. We conclude that in the absence of aldosterone, mice can conserve Na+ without ENaC activation but at the expense of diminished glomerular filtration rate. Excretion of a K+ load can be accomplished through aldosterone-independent upregulation of ENaC, but aldosterone is required to excrete the excess K+ without hyperkalemia.

Journal

American Journal of Physiology-Renal Physiology – The American Physiological Society

Published: Aug 1, 2020

References

  • Clinical appraisal of creatinine clearance as a measurement of glomerular filtration rate
    Bauer, JH; Brooks, CS; Burch, RN
  • Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line
    Bens, M; Vallet, V; Cluzeaud, F; Pascual-Letallec, L; Kahn, A; Rafestin-Oblin, ME; Rossier, BC; Vandewalle, A
  • Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone
    Chiga, M; Rai, T; Yang, SS; Ohta, A; Takizawa, T; Sasaki, S; Uchida, S
  • Action of aldosterone on the bladder and skin of the toad
    Crabbé, J; Deweer, P
  • Regulation of maturation and processing of ENaC subunits in the rat kidney
    Ergonul, Z; Frindt, G; Palmer, LG
  • Surface expression of epithelial Na channel protein in rat kidney
    Frindt, G; Ergonul, Z; Palmer, LG
  • Regulation of ENaC trafficking in rat kidney
    Frindt, G; Gravotta, D; Palmer, LG
  • Regulation of epithelial Na+ channels by adrenal steroids: mineralocorticoid and glucocorticoid effects
    Frindt, G; Palmer, LG
  • Acute effects of aldosterone on the epithelial Na channel in rat kidney
    Frindt, G; Palmer, LG
  • Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na+ delivery
    Frindt, G; Yang, L; Bamberg, K; Palmer, LG
  • Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia
    Frindt, G; Yang, L; Uchida, S; Weinstein, AM; Palmer, LG
  • Mineralocorticoid versus glucocorticoid receptor occupancy mediating aldosterone-stimulated sodium transport in a novel renal cell line
    Gaeggeler, H-P; Gonzalez-Rodriguez, E; Jaeger, NF; Loffing-Cueni, D; Norregaard, R; Loffing, J; Horisberger, J-D; Rossier, BC
  • Salt balance and long-term blood pressure control
    Guyton, AC; Coleman, TG; Young, DB; Lohmeier, TE; DeClue, JW
  • Acute inhibition of NCC does not activate distal electrogenic Na+ reabsorption or kaliuresis
    Hunter, RW; Craigie, E; Homer, NZ; Mullins, JJ; Bailey, MA
  • Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice
    Lee, G; Makhanova, N; Caron, K; Lopez, ML; Gomez, RA; Smithies, O; Kim, HS
  • Serum creatinine and renal function
    Levey, AS; Perrone, RD; Madias, NE
  • Kidney function in mice lacking aldosterone
    Makhanova, N; Lee, G; Takahashi, N; Sequeira Lopez, ML; Gomez, RA; Kim, HS; Smithies, O
  • Disturbed homeostasis in sodium-restricted mice heterozygous and homozygous for aldosterone synthase gene disruption
    Makhanova, N; Sequeira-Lopez, MLS; Gomez, RA; Kim, HS; Smithies, O
  • Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure
    McDonough, AA
  • Tissue kallikrein permits early renal adaptation to potassium load
    El Moghrabi, S; Houillier, P; Picard, N; Sohet, F; Wootla, B; Bloch-Faure, M; Leviel, F; Cheval, L; Frische, S; Meneton, P; Eladari, D; Chambrey, R
  • Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron
    Nesterov, V; Dahlmann, A; Krueger, B; Bertog, M; Loffing, J; Korbmacher, C
  • Differential regulation of Na+ transporters along nephron during ANG II-dependent hypertension: distal stimulation counteracted by proximal inhibition
    Nguyen, MTX; Lee, DH; Delpire, E; McDonough, AA
  • Regulation of Na channels of the rat cortical collecting tubule by aldosterone
    Pácha, J; Frindt, G; Antonian, L; Silver, RB; Palmer, LG
  • Regulation of apical K and Na channels and Na/K pumps in rat cortical collecting tubule by dietary K
    Palmer, LG; Antonian, L; Frindt, G
  • Cl− channels of the distal nephron
    Palmer, LG; Frindt, G
  • Tissue kallikrein activation of the epithelial Na channel
    Patel, AB; Chao, J; Palmer, LG
  • Extracellular K+ rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl−-dependent and independent mechanisms
    Penton, D; Czogalla, J; Wengi, A; Himmerkus, N; Loffing-Cueni, D; Carrel, M; Rajaram, RD; Staub, O; Bleich, M; Schweda, F; Loffing, J
  • Aldosterone and potassium homeostasis
    Rabinowitz, L
  • Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis
    Rengarajan, S; Lee, DH; Oh, YT; Delpire, E; Youn, JH; McDonough, AA
  • A high-throughput method for measurement of glomerular filtration rate in conscious mice
    Rieg, T
  • Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited
    Rossier, BC; Baker, ME; Studer, RA
  • Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism
    Sebastian, A; Schambelan, M; Lindenfeld, S; Morris, RC
  • A quantitative method for the bioassay of the effect of adrenal cortical steroids on mineral metabolism
    Simpson, SA; Tait, JF; Woodford, M; Graves, S
  • Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice
    Sorensen, MV; Grossmann, S; Roesinger, M; Gresko, N; Todkar, AP; Barmettler, G; Ziegler, U; Odermatt, A; Loffing-Cueni, D; Loffing, J
  • Potassium acts through mTOR to regulate its own secretion
    Sørensen, MV; Saha, B; Jensen, IS; Wu, P; Ayasse, N; Gleason, CE; Svendsen, SL; Wang, WH; Pearce, D
  • Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney
    Stanton, B; Pan, L; Deetjen, H; Guckian, V; Giebisch, G
  • Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride
    Terker, AS; Zhang, C; McCormick, JA; Lazelle, RA; Zhang, C; Meermeier, NP; Siler, DA; Park, HJ; Fu, Y; Cohen, DM; Weinstein, AM; Wang, WH; Yang, CL; Ellison, DH
  • Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency
    Todkar, A; Picard, N; Loffing-Cueni, D; Sorensen, MV; Mihailova, M; Nesterov, V; Makhanova, N; Korbmacher, C; Wagner, CA; Loffing, J
  • Expression and phosphorylation of the Na+-Cl− cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1
    Vallon, V; Schroth, J; Lang, F; Kuhl, D; Uchida, S
  • Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone
    van der Lubbe, N; Lim, CH; Fenton, RA; Meima, ME; Jan Danser, AH; Zietse, R; Hoorn, EJ
  • Mineralocorticoid action in the aldosterone-sensitive distal nephron
    Verrey, F; Hummler, E; Schild, L; Rossier, BC; Alpern, RJ; Hebert, SC
  • Sodium and chloride transport: proximal nephron
    Weinstein, AM; Alpern, RJ; Hebert, SC
  • Regulation of potassium secretion
    Wright, FS; Giebisch, G; Seldin, DW; Giebisch, G
  • SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone
    Yang, L; Frindt, G; Lang, F; Kuhl, D; Vallon, V; Palmer, LG
  • SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction
    Yang, SS; Lo, YF; Wu, CC; Lin, SW; Yeh, CJ; Chu, P; Sytwu, HK; Uchida, S; Sasaki, S; Lin, SH