title: The Trade-Off between Dietary Salt and Cardiovascular Disease; A Role for Na/K-ATPase Signaling?
abstract: It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathways. This review will discuss the mechanism of CTS in renal sodium handling and a potential "trade-off" effect from their role in inducing tissue fibrosis.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine , Aurora, CO , USA.
authors.forename: Joe X
authors.initials: JX
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of Toledo College of Medicine , Toledo, OH , USA.
authors.forename: Anna Pearl
authors.initials: AP
authors.lastname: Shapiro
authors.affiliation: Department of Medicine, Joan C. Edwards School of Medicine, Marshall University , Huntington, WV , USA.
authors.forename: Joseph Isaac
authors.initials: JI
authors.lastname: Shapiro
keywords: cardiotonic steroids; digitalis-like factors; fibrosis; hypertension; renal failure; signaling; sodium pump
references.citation: Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2026-34
references.pmid: 19837951
references.citation: Adv Intern Med. 1987;32:1-25
references.pmid: 2950729
references.citation: Am J Cardiovasc Drugs. 2007;7(3):173-89
references.pmid: 17610345
references.citation: Biochim Biophys Acta. 1957 Feb;23(2):394-401
references.pmid: 13412736
references.citation: Nephrol Dial Transplant. 2011 Sep;26(9):2912-9
references.pmid: 21292813
references.citation: J Biol Chem. 2007 Apr 6;282(14):10585-93
references.pmid: 17296611
references.citation: J Pharmacol Exp Ther. 1981 Jun;217(3):784-90
references.pmid: 6262496
references.citation: Circulation. 1999 Mar 9;99(9):1265-70
references.pmid: 10069797
references.citation: Eur J Biochem. 2002 May;269(10):2434-9
references.pmid: 12027880
references.citation: Ann N Y Acad Sci. 1992 Nov 30;671:156-68; discussion 168-9
references.pmid: 1337670
references.citation: Hypertension. 2009 Dec;54(6):1313-20
references.pmid: 19884563
references.citation: J Biol Chem. 2013 Nov 22;288(47):34249-34258
references.pmid: 24121502
references.citation: Yale J Biol Med. 1975 Sep;48(4):293-303
references.pmid: 1202759
references.citation: Am J Obstet Gynecol. 1984 Sep 1;150(1):83-5
references.pmid: 6540989
references.citation: Am J Physiol Renal Physiol. 2009 May;296(5):F1219-26
references.pmid: 19261738
references.citation: Mol Biol Cell. 2006 Jan;17(1):317-26
references.pmid: 16267270
references.citation: Adv Nephrol Necker Hosp. 1971;1:97-111
references.pmid: 5006262
references.citation: Clin Biochem. 1981 Apr;14(2):67-71
references.pmid: 7296815
references.citation: Jpn Circ J. 1986 Jul;50(7):628-35
references.pmid: 3773229
references.citation: Am J Hypertens. 2014 Apr;27(4):603-9
references.pmid: 24014658
references.citation: Am J Physiol Renal Physiol. 2006 May;290(5):F997-1008
references.pmid: 16352745
references.citation: Mol Cell Biochem. 2003 Jan;242(1-2):181-7
references.pmid: 12619881
references.citation: Clin Pharm. 1986 Oct;5(10):810-6
references.pmid: 3780148
references.citation: Biochem Soc Trans. 1978;6(5):837-9
references.pmid: 744329
references.citation: Cell Mol Biol (Noisy-le-grand). 2001 Mar;47(2):383-90
references.pmid: 11357899
references.citation: Cell Mol Biol (Noisy-le-grand). 2006 Dec 30;52(8):3-14
references.pmid: 17535729
references.citation: J Am Soc Nephrol. 2008 Oct;19(10):1947-54
references.pmid: 18667729
references.citation: J Am Soc Nephrol. 1990 Dec;1(6):927-8
references.pmid: 2151752
references.citation: Nature. 1980 Oct 23;287(5784):743-5
references.pmid: 6253813
references.citation: Kidney Int. 2001 Dec;60(6):2367-76
references.pmid: 11737612
references.citation: J Clin Invest. 1974 Jun;53(6):1559-67
references.pmid: 4830222
references.citation: Mol Pharmacol. 2010 Jun;77(6):961-7
references.pmid: 20335388
references.citation: Acta Pharmacol Toxicol (Copenh). 1979 Jul;45(1):66-72
references.pmid: 474161
references.citation: Am J Physiol Cell Physiol. 2008 Feb;294(2):C555-63
references.pmid: 18077602
references.citation: Clin Sci. 1968 Feb;34(1):57-72
references.pmid: 5643327
references.citation: Am J Physiol Renal Physiol. 2009 Apr;296(4):F922-34
references.pmid: 19176701
references.citation: Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1833-9
references.pmid: 19376809
references.citation: Nephrology (Carlton). 2010 Jun;15 Suppl 2:49-52
references.pmid: 20586949
references.citation: Annu Rev Physiol. 1972;34:13-46
references.pmid: 4334846
references.citation: Pediatr Res. 1986 Jan;20(1):28-31
references.pmid: 3511439
references.citation: J Biol Chem. 2011 Jul 1;286(26):22806-13
references.pmid: 21555512
references.citation: Adv Intern Med. 1994;39:23-47
references.pmid: 8140955
references.citation: Proc Soc Exp Biol Med. 1984 Jun;176(2):123-31
references.pmid: 6326156
references.citation: Hypertension. 1982 Sep-Oct;4(5 Pt 2):III14-9
references.pmid: 7049928
references.citation: Kidney Int. 1982 Feb;21(2):339-44
references.pmid: 7200165
references.citation: N Engl J Med. 1997 Apr 17;336(16):1117-24
references.pmid: 9099655
references.citation: Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H1972-3
references.pmid: 19855053
references.citation: Kidney Int. 2005 May;67(5):1868-77
references.pmid: 15840034
references.citation: Biochim Biophys Acta. 2010 Dec;1802(12):1254-8
references.pmid: 20083196
references.citation: J Biol Chem. 1999 Jul 2;274(27):19323-8
references.pmid: 10383443
references.citation: Kidney Int. 2005 May;67(5):1844-54
references.pmid: 15840032
references.citation: Pathophysiology. 2007 Dec;14(3-4):171-81
references.pmid: 17961998
references.citation: J Biol Chem. 2008 Jan 11;283(2):1128-36
references.pmid: 17993456
references.citation: Life Sci. 1983 Jul 18;33(3):297-302
references.pmid: 6223192
references.citation: Hypertension. 2007 Jan;49(1):215-24
references.pmid: 17145984
references.citation: Anal Biochem. 1989 Dec;183(2):215-9
references.pmid: 2560348
references.citation: Mol Biol Cell. 2005 Sep;16(9):4034-45
references.pmid: 15975899
references.citation: Biochim Biophys Acta. 1996 Feb 21;1279(1):43-8
references.pmid: 8624359
references.citation: Cardiovasc Res. 2007 Feb 1;73(3):488-96
references.pmid: 17157283
references.citation: Pharmacol Rev. 2009 Mar;61(1):9-38
references.pmid: 19325075
references.citation: Biosci Rep. 1998 Aug;18(4):155-69
references.pmid: 9877230
references.citation: Biosci Rep. 2004 Aug-Oct;24(4-5):436-51
references.pmid: 16134021
references.citation: Clin Chim Acta. 2014 Apr 20;431:87-92
references.pmid: 24508998
references.citation: J Biol Chem. 2004 Dec 24;279(52):54053-61
references.pmid: 15485817
references.citation: Clin Biochem. 2005 Jan;38(1):36-45
references.pmid: 15607315
references.citation: J Physiol. 1968 May;196(2):121P-122P
references.pmid: 5652862
references.citation: Kidney Int. 2003 May;63(5):1785-90
references.pmid: 12675854
references.citation: Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6259-63
references.pmid: 1648735
references.citation: Life Sci. 1981 Jan 5;28(1):89-94
references.pmid: 7219045
references.citation: J Clin Invest. 1951 Nov;30(11):1250-61
references.pmid: 14888703
references.citation: Hypertension. 2006 Mar;47(3):488-95
references.pmid: 16446397
references.citation: Am J Physiol Renal Physiol. 2008 Feb;294(2):F450-4
references.pmid: 18032546
references.citation: Am J Hypertens. 2012 Jun;25(6):690-6
references.pmid: 22378033
references.citation: Am J Physiol. 1966 Jan;210(1):162-8
references.pmid: 5903137
references.citation: J Biol Chem. 2002 May 24;277(21):18694-702
references.pmid: 11907028
references.citation: Physiology (Bethesda). 2008 Aug;23:205-11
references.pmid: 18697994
references.citation: J Hum Hypertens. 1989 Oct;3(5):289-98
references.pmid: 2681780
references.citation: Kidney Int Suppl. 1978 Jun;(8):S5-8
references.pmid: 278898
references.citation: J Bioenerg Biomembr. 1992 Jun;24(3):249-61
references.pmid: 1328174
references.citation: J Clin Invest. 1970 May;49(5):926-35
references.pmid: 5441546
references.citation: Clin Sci Mol Med. 1977 Oct;53(4):329-34
references.pmid: 144041
references.citation: Nat Clin Pract Nephrol. 2008 Jul;4(7):378-92
references.pmid: 18542120
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R529-35
references.pmid: 16467500
references.citation: Biochim Biophys Acta. 2010 Dec;1802(12):1230-6
references.pmid: 20347967
references.citation: J Biol Chem. 2001 Jun 15;276(24):20839-48
references.pmid: 11278621
references.citation: N Engl J Med. 1972 May 18;286(20):1093-9
references.pmid: 4553202
references.citation: Hypertension. 1994 Nov;24(5):640-4
references.pmid: 7960026
references.citation: Kidney Int. 2004 Jul;66(1):227-41
references.pmid: 15200429
references.citation: J Biol Chem. 2000 Sep 8;275(36):27832-7
references.pmid: 10874030
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R524-8
references.pmid: 16467499
references.citation: Front Biosci. 2005 Sep 01;10:3100-9
references.pmid: 15970564
references.citation: Kidney Int. 2002 Dec;62(6):2118-25
references.pmid: 12427136
references.citation: J Biol Chem. 1985 Sep 25;260(21):11396-405
references.pmid: 2995332
references.citation: Am J Physiol. 1986 Jul;251(1 Pt 2):H205-9
references.pmid: 3014905
references.citation: Cell Biochem Biophys. 2006;46(3):303-16
references.pmid: 17272855
references.citation: J Biol Chem. 2004 Apr 23;279(17):17250-9
references.pmid: 14963033
references.citation: Clin Sci. 1961 Oct;21:249-58
references.pmid: 13884596
references.citation: Biochim Biophys Acta. 1959 Oct;35:324-33
references.pmid: 13831537
references.citation: J Biol Chem. 2000 Sep 8;275(36):27838-44
references.pmid: 10874029
references.citation: J Clin Invest. 1987 Sep;80(3):698-705
references.pmid: 2957391
references.citation: Genomics. 1988 Feb;2(2):128-38
references.pmid: 2842249
references.citation: J Biol Chem. 2011 Sep 16;286(37):32394-403
references.pmid: 21784855