Low Na, high K diet and the role of aldosterone in BK-mediated K excretion.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Diet*; Aldosterone/*metabolism ; Large-Conductance Calcium-Activated Potassium Channels/*metabolism ; Potassium/*pharmacokinetics ; Potassium/*pharmacology ; Sodium/*pharmacology; Animals ; Cardiovascular Diseases/diet therapy ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Mice

A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular (CV) disease in many societies. Part of the benefit of LNaHK relies on its diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not understood. LNaHK mice exhibit an increase in renal K secretion that is dependent on the large, Ca-activated K channel, (BK-α with accessory BK-β4; BK-α/β4). We hypothesized that aldo causes an osmotic diuresis by increasing BK-α/β4-mediated K secretion in LNaHK mice. We found that the plasma aldo concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham), adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate, transtubular K gradient (TTKG), and BK-α and BK-β4 expressions, were decreased in ADX-LA, but not different in ADX-HA. BK-β4 knockout (β4KO) and WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in sham and ADX-HA, the K clearance and TTKG of β4KO were less than WT. In response to amiloride treatment, the osmolar clearance was increased in WT Con, decreased in WT LNaHK, and unchanged in β4KO LNaHK. These data show that the high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-α/β4-mediated K secretion, which creates an osmotic diuresis that may contribute to a reduction in CV disease.

J Clin Invest. 1982 Aug;70(2):219-29. (PMID: 6284797)
Am J Physiol. 1981 Jun;240(6):F536-44. (PMID: 6264796)
J Clin Invest. 1984 Nov;74(5):1792-802. (PMID: 6501571)
Am J Physiol Renal Physiol. 2009 Aug;297(2):F389-96. (PMID: 19474187)
J Am Soc Nephrol. 2010 Apr;21(4):634-45. (PMID: 20299355)
Kidney Int. 2010 Nov;78(10):956-62. (PMID: 20720523)
Physiology (Bethesda). 2011 Apr;26(2):115-23. (PMID: 21487030)
Am J Physiol Renal Physiol. 2011 Jun;300(6):F1319-26. (PMID: 21454249)
Am J Physiol Renal Physiol. 2011 Jun;300(6):F1385-93. (PMID: 21454252)
Clin Exp Nephrol. 2011 Jun;15(3):355-62. (PMID: 21347582)
N Engl J Med. 1985 Jan 31;312(5):283-9. (PMID: 2981409)
Am J Physiol. 1985 Jun;248(6 Pt 2):F858-68. (PMID: 4003557)
Pflugers Arch. 1987 Jun;409(1-2):126-31. (PMID: 3039448)
Clin Exp Pharmacol Physiol. 1994 Apr;21(4):315-8. (PMID: 7923898)
Am J Physiol. 1996 Jul;271(1 Pt 2):F7-15. (PMID: 8760237)
Am J Physiol. 1996 Jan;270(1 Pt 2):F211-9. (PMID: 8769842)
Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14552-7. (PMID: 9826738)
Pflugers Arch. 1999 Aug;438(3):354-60. (PMID: 10398866)
J Clin Invest. 1999 Oct;104(7):R19-23. (PMID: 10510339)
Physiol Rev. 2005 Jan;85(1):319-71. (PMID: 15618483)
Kidney Int. 2006 Jul;70(1):51-9. (PMID: 16710355)
Kidney Int. 2007 Sep;72(5):529-30. (PMID: 17713560)
J Endocrinol. 2008 Feb;196(2):215-24. (PMID: 18252945)
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11800-5. (PMID: 19556540)
Am J Physiol Renal Physiol. 2009 Aug;297(2):F420-8. (PMID: 19458125)
Cardiovasc Drugs Ther. 2011 Dec;25 Suppl 1:S67-76. (PMID: 22120095)
Mol Cell Endocrinol. 2012 Mar 24;350(2):223-34. (PMID: 21801805)
Am J Physiol Renal Physiol. 2012 Nov 1;303(9):F1289-99. (PMID: 22933298)
Am J Physiol Renal Physiol. 2012 Dec 1;303(11):F1563-71. (PMID: 22993067)
Kidney Int. 2013 May;83(5):811-24. (PMID: 23447069)
Am J Physiol Renal Physiol. 2013 Aug 15;305(4):F463-76. (PMID: 23761673)
Semin Nephrol. 2013 May;33(3):215-28. (PMID: 23953799)
Eur J Gastroenterol Hepatol. 2013 Sep;25(9):1086-92. (PMID: 23524523)
Curr Opin Pharmacol. 2014 Apr;15:28-32. (PMID: 24721651)
Am J Physiol Renal Physiol. 2014 May 1;306(9):F1059-68. (PMID: 24598799)
Kidney Int. 2014 Jul;86(1):139-45. (PMID: 24573316)
J Am Soc Nephrol. 2015 Feb;26(2):425-38. (PMID: 25071088)
Am J Clin Nutr. 2005 Feb;81(2):341-54. (PMID: 15699220)
Nature. 2000 Oct 19;407(6806):870-6. (PMID: 11057658)
Circ Res. 2000 Nov 24;87(11):E53-60. (PMID: 11090555)
Eur J Nutr. 2001 Oct;40(5):200-13. (PMID: 11842945)
J Biol Chem. 2003 Jun 20;278(25):23066-75. (PMID: 12684516)
Arq Bras Cardiol. 2003 Mar;80(3):289-300. (PMID: 12856272)
J Clin Invest. 2003 Sep;112(5):717-24. (PMID: 12952920)
Nat Cell Biol. 2003 Oct;5(10):902-6. (PMID: 14515130)
J Am Soc Nephrol. 2004 Mar;15(3):558-65. (PMID: 14978157)
J Am Soc Nephrol. 2004 Apr;15(4):885-91. (PMID: 15034090)
J Clin Invest. 2004 Apr;113(7):1032-9. (PMID: 15057310)
Kidney Int. 2004 May;65(5):1959-67. (PMID: 15086941)
N Engl J Med. 2004 Jul 1;351(1):33-41. (PMID: 15229305)
Am J Pathol. 1969 Nov;57(2):335-64. (PMID: 4311762)
J Clin Invest. 1970 Sep;49(9):1724-36. (PMID: 5449709)
Circulation. 1975 Jul;52(1):146-51. (PMID: 1132118)
Hypertension. 1983 Nov-Dec;5(6):864-72. (PMID: 6360869)

R01 DK071014 United States DK NIDDK NIH HHS; R01 DK073070 United States DK NIDDK NIH HHS; R01 DK092474 United States DK NIDDK NIH HHS

0 (Large-Conductance Calcium-Activated Potassium Channels)
4964P6T9RB (Aldosterone)
9NEZ333N27 (Sodium)
RWP5GA015D (Potassium)

Date Created: 20150122 Date Completed: 20151228 Latest Revision: 20190223

20221213

PMC4301648

10.1371/journal.pone.0115515

25607984