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Understanding the Two Faces of Low-Salt Intake

  • Hypertension and Obesity (E Reisin, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Fierce debate has developed whether low-sodium intake, like high-sodium intake, could be associated with adverse outcome. The debate originates in earlier epidemiological studies associating high-sodium intake with high blood pressure and more recent studies demonstrating a higher cardiovascular event rate with both low- and high-sodium intake. This brings into question whether we entirely understand the consequences of high- and (very) low-sodium intake for the systemic hemodynamics, the kidney function, the vascular wall, the immune system, and the brain. Evolutionarily, sodium retention mechanisms in the context of low dietary sodium provided a survival advantage and are highly conserved, exemplified by the renin-angiotensin system. What is the potential for this sodium-retaining mechanism to cause harm? In this paper, we will consider current views on how a sodium load is handled, visiting aspects including the effect of sodium on the vessel wall, the sympathetic nervous system, the brain renin-angiotensin system, the skin as “third compartment” coupling to vascular endothelial growth factor C, and the kidneys. From these perspectives, several mechanisms can be envisioned whereby a low-sodium diet could potentially cause harm, including the renin-angiotensin system and the sympathetic nervous system. Altogether, the uncertainties preclude a unifying model or practical clinical guidance regarding the effects of a low-sodium diet for an individual. There is a very strong need for fundamental and translational studies to enhance the understanding of the potential adverse consequences of low-salt intake as an initial step to facilitate better clinical guidance.

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Abbreviations

ADH:

anti-diuretic hormone

AGTR1:

angiotensin receptor 1 gene

ANG II:

angiotensin II

ANG(1-7):

angiotensin (1-7)

ANP:

atrial natriuretic peptide

AP:

area postrema

ARNA:

afferent renal nerve activity

AT1aR:

angiotensin II receptor type 1a

AT1R:

angiotensin II receptor type 1

AT2R:

angiotensin II receptor type 2

BP:

blood pressure

CKD:

chronic kidney disease

CNS:

central nervous system

CSF:

cerebrospinal fluid

CVD:

cardiovascular disease

CVO:

circumventricular organ

DASH:

Dietary Approaches to Stop Hypertension

ECFV:

extracellular fluid volume

ENaC:

epithelial sodium channel

eNOS:

endothelial nitric oxide synthase

ET:

endothelin

GAGs:

glycosaminoglycans

GFR:

glomerular filtration rate

L-NMMA:

NG-Monomethyl-L-arginine

MR:

mineralocorticoid receptor

NHE3:

sodium hydrogen exchanger 3

NKCC2:

sodium potassium chloride co-transporter

NO:

nitric oxide

NTS:

nucleus tractus solitarius

OVLT:

organum vasculosum of the lamina terminalis

PURE:

Prospective Urban Rural

PVN:

paraventricular nucleus

RAS:

renin angiotensin system

RBF:

renal blood flow

RVLM:

rostro-ventrolateral medulla

SFO:

subfornical organ

SHR:

spontaneously hypertensive rat

SNS:

sympathetic nervous system

TGF-β:

Transforming Growth Factor β

TNF-α:

Tumor Necrosis Factor α

TOHP:

Trials of Hypertension Prevention

TONEBP/NFAT5:

tonicity-responsive enhancer- binding protein

VEGF-C:

vascular endothelial growth factor C

VSMC:

vascular smooth muscle cell

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerova J, Richart T, et al. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011;305(17):1777–85. doi:10.1001/jama.2011.574.

    Article  CAS  PubMed  Google Scholar 

  2. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ. 1988;297(6644):319–28.

  3. Drueke TB. Salt and health: time to revisit the recommendations. Kidney Int. 2016;89(2):259–60. doi:10.1016/j.kint.2015.12.009.

    Article  CAS  PubMed  Google Scholar 

  4. Guyton AC. Renal function curve—a key to understanding the pathogenesis of hypertension. Hypertension. 1987;10(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  5. O'Donnell M, Mente A, Rangarajan S, McQueen MJ, Wang X, Liu L, et al. Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med. 2014;371(7):612–23. doi:10.1056/NEJMoa1311889.

    Article  PubMed  CAS  Google Scholar 

  6. Campese VM. Salt sensitivity in hypertension. Renal and cardiovascular implications. Hypertension. 1994;23(4):531–50.

    Article  CAS  PubMed  Google Scholar 

  7. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. DASH-sodium collaborative research group. N Engl J Med. 2001;344(1):3–10. doi:10.1056/NEJM200101043440101.

    Article  CAS  PubMed  Google Scholar 

  8. Whelton PK, Appel L, Charleston J, et al. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. JAMA. 1992;267(9):1213–20. doi:10.1001/jama.1992.03480090061028.

  9. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. Arch Intern Med. 1997;157(6):657–67. doi:10.1001/archinte.1997.00440270105009.

  10. •• Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 2007;334(7599):885–8. doi:10.1136/bmj.39147.604896.55. This study shows that intensive lifestyle interventions including a low sodium diet are effective in reducing long term cardiovascular events.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease: a meta-analysis of randomized controlled trials (Cochrane review). Am J Hypertens. 2011;24(8):843–53. doi:10.1038/ajh.2011.115.

    Article  CAS  PubMed  Google Scholar 

  12. Alderman MH, Cohen H, Madhavan S. Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I). Lancet. 1998;351(9105):781–5. doi:10.1016/S0140-6736(97)09092-2.

    Article  CAS  PubMed  Google Scholar 

  13. Titze J, Machnik A. Sodium sensing in the interstitium and relationship to hypertension. Curr Opin Nephrol Hypertens. 2010;19(4):385–92. doi:10.1097/MNH.0b013e32833aeb3b.

    Article  PubMed  Google Scholar 

  14. Spencer AG, Greasley PJ. Pharmacologic inhibition of intestinal sodium uptake: a gut centric approach to sodium management. Curr Opin Nephrol Hypertens. 2015;24(5):410–6. doi:10.1097/MNH.0000000000000154.

    Article  CAS  PubMed  Google Scholar 

  15. •• Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? I—analysis of observational data among populations. BMJ. 1991;302(6780):811–5. Describes strking differences among countries regarding daily sodium intake.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Frost CD, Law MR, Wald NJ. By how much does dietary salt reduction lower blood pressure? II—analysis of observational data within populations. BMJ. 1991;302(6780):815–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? III—analysis of data from trials of salt reduction. BMJ. 1991;302(6780):819–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Castiglioni P, Parati G, Lazzeroni D, Bini M, Faini A, Brambilla L et al. Hemodynamic and Autonomic Response to Different Salt Intakes in Normotensive Individuals. J Am Heart Assoc. 2016;5(8):e003736. doi:10.1161/JAHA.116.003736.

  19. Schmidlin O, Sebastian AF, Morris RC Jr. What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks. Hypertension. 2007;49(5):1032–9. doi:10.1161/HYPERTENSIONAHA.106.084640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dahl LK, Heine M. Primary role of renal homografts in setting chronic blood pressure levels in rats. Circ Res. 1975;36(6):692–6.

    Article  CAS  PubMed  Google Scholar 

  21. Morgan DA, DiBona GF, Mark AL. Effects of interstrain renal transplantation on NaCl-induced hypertension in Dahl rats. Hypertension. 1990;15(4):436–42.

    Article  CAS  PubMed  Google Scholar 

  22. Thomas B, Taber DJ, Srinivas TR. Hypertension after kidney transplantation: a pathophysiologic approach. Curr Hypertens Rep. 2013;15(5):458–69. doi:10.1007/s11906-013-0381-0.

    Article  CAS  PubMed  Google Scholar 

  23. • Smallegange C, Hale TM, Bushfield TL, Adams MA. Persistent lowering of pressure by transplanting kidneys from adult spontaneously hypertensive rats treated with brief antihypertensive therapy. Hypertension. 2004;44(1):89–94. doi:10.1161/01.HYP.0000129539.88028.e6. An Exreme example of 'hypertension follows the kidney': temporary treatment of hypertensive rats resulted in a long term decrease in BP, and transplantaion of the kidneys into other hypertensive animals decreased their BP.

    Article  CAS  PubMed  Google Scholar 

  24. He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ. 2013;346:f1325. doi:10.1136/bmj.f1325.

    Article  PubMed  Google Scholar 

  25. Karppanen H, Mervaala E. Sodium intake and hypertension. Prog Cardiovasc Dis. 2006;49(2):59–75. doi:10.1016/j.pcad.2006.07.001.

    Article  CAS  PubMed  Google Scholar 

  26. Heck GL, Mierson S, DeSimone JA. Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science. 1984;223(4634):403–5.

    Article  CAS  PubMed  Google Scholar 

  27. Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJ, et al. The cells and peripheral representation of sodium taste in mice. Nature. 2010;464(7286):297–301. doi:10.1038/nature08783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Okiyama A, Torii K, Tordoff MG. Increased NaCl preference of rats fed low-protein diet. Am J Phys. 1996;270(6 Pt 2):R1189–96.

    CAS  Google Scholar 

  29. Pereira-Derderian DT, Vendramini RC, Menani JV, De Luca LA, Jr. Water deprivation-induced sodium appetite and differential expression of encephalic c-Fos immunoreactivity in the spontaneously hypertensive rat. Am J Physiol Regul Integr Comp Physiol. 2010;298(5):R1298–309. doi:10.1152/ajpregu.00359.2009.

    Article  CAS  PubMed  Google Scholar 

  30. Johnson AK, Thunhorst RL. The neuroendocrinology of thirst and salt appetite: visceral sensory signals and mechanisms of central integration. Front Neuroendocrinol. 1997;18(3):292–353. doi:10.1006/frne.1997.0153.

    Article  CAS  PubMed  Google Scholar 

  31. Johnson AK, Gross PM. Sensory circumventricular organs and brain homeostatic pathways. FASEB J. 1993;7(8):678–86.

    CAS  PubMed  Google Scholar 

  32. Tamura R, Norgren R. Repeated sodium depletion affects gustatory neural responses in the nucleus of the solitary tract of rats. Am J Phys. 1997;273(4 Pt 2):R1381–91.

    CAS  Google Scholar 

  33. Fitzsimons JT. Angiotensin, thirst, and sodium appetite. Physiol Rev. 1998;78(3):583–686.

    CAS  PubMed  Google Scholar 

  34. Fu Y, Vallon V. Mineralocorticoid-induced sodium appetite and renal salt retention: evidence for common signaling and effector mechanisms. Nephron Physiol. 2014;128(1–2):8–16. doi:10.1159/000368264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nicholls MG, Kiowski W, Zweifler AJ, Julius S, Schork MA, Greenhouse J. Plasma norepinephrine variations with dietary sodium intake. Hypertension. 1980;2(1):29–32.

    Article  CAS  PubMed  Google Scholar 

  36. Oka Y, Butnaru M, von Buchholtz L, Ryba NJ, Zuker CS. High salt recruits aversive taste pathways. Nature. 2013;494(7438):472–5. doi:10.1038/nature11905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Spencer AG, Labonte ED, Rosenbaum DP, Plato CF, Carreras CW, Leadbetter MR, et al. Intestinal inhibition of the Na+/H+ exchanger 3 prevents cardiorenal damage in rats and inhibits Na+ uptake in humans. Sci Transl Med. 2014;6(227):227ra36. doi:10.1126/scitranslmed.3007790.

    Article  PubMed  CAS  Google Scholar 

  38. Cho JH, Musch MW, Bookstein CM, McSwine RL, Rabenau K, Chang EB. Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3 expression of the proximal colon. Am J Phys. 1998;274(3 Pt 1):C586–94.

    CAS  Google Scholar 

  39. Gerritsen KG, Boer WH, Joles JA. The importance of intake: a gut feeling. Ann Transl Med. 2015;3(4):49. doi:10.3978/j.issn.2305-5839.2015.03.21.

    PubMed  PubMed Central  Google Scholar 

  40. Johansson S, Rosenbaum DP, Knutsson M, Leonsson-Zachrisson M. A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers. Clin Exp Nephrol. 2016; doi:10.1007/s10157-016-1302-8.

    PubMed  Google Scholar 

  41. • Guyton AC. Dominant role of the kidneys and accessory role of whole-body autoregulation in the pathogenesis of hypertension. Am J Hypertens. 1989;2(7):575–85. All time classic on the BP regulation.

    Article  CAS  PubMed  Google Scholar 

  42. Kurtz TW, DiCarlo SE, Pravenec M, Schmidlin O, Tanaka M, Morris RC Jr. An alternative hypothesis to the widely held view that renal excretion of sodium accounts for resistance to salt-induced hypertension. Kidney Int. 2016;90(5):965–73. doi:10.1016/j.kint.2016.05.032.

    Article  CAS  PubMed  Google Scholar 

  43. Titze J, Shakibaei M, Schafflhuber M, Schulze-Tanzil G, Porst M, Schwind KH, et al. Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin. Am J Physiol Heart Circ Physiol. 2004;287(1):H203–8. doi:10.1152/ajpheart.01237.2003.

    Article  CAS  PubMed  Google Scholar 

  44. Titze J, Lang R, Ilies C, Schwind KH, Kirsch KA, Dietsch P, et al. Osmotically inactive skin Na+ storage in rats. Am J Physiol Renal Physiol. 2003;285(6):F1108–17. doi:10.1152/ajprenal.00200.2003.

    Article  CAS  PubMed  Google Scholar 

  45. •• Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15(5):545–52. doi:10.1038/nm.1960. This paper demonstrates a link between sodium loading, sodium storage in the skin and blood pressure regulation via VEGF-C.

    Article  CAS  PubMed  Google Scholar 

  46. Braam B. Renal endothelial and macula densa NOS: integrated response to changes in extracellular fluid volume. Am J Phys. 1999;276(6 Pt 2):R1551–61.

    CAS  Google Scholar 

  47. Gennari-Moser C, Escher G, Kramer S, Dick B, Eisele N, Baumann M, et al. Normotensive blood pressure in pregnancy: the role of salt and aldosterone. Hypertension. 2014;63(2):362–8. doi:10.1161/HYPERTENSIONAHA.113.02320.

    Article  CAS  PubMed  Google Scholar 

  48. Wong F, Logan A, Blendis L. The effect of varying sodium intake on blood volume, forearm blood flow and vascular responsiveness to sympathetic stimulation in pre-ascitic cirrhosis. Clin Invest Med. 1996;19(3):184–94.

    CAS  PubMed  Google Scholar 

  49. Doi Y, Nose H, Morimoto T. Changes in Na concentration in cerebrospinal fluid during acute hypernatremia and their effect on drinking in juvenile rats. Physiol Behav. 1992;52(3):499–504.

    Article  CAS  PubMed  Google Scholar 

  50. Andersson B. Regulation of water intake. Physiol Rev. 1978;58(3):582.

    CAS  PubMed  Google Scholar 

  51. Weisinger RS, Considine P, Denton DA, Leksell L, McKinley MJ, Mouw DR, et al. Role of sodium concentration of the cerebrospinal fluid in the salt appetite of sheep. Am J Phys. 1982;242(1):R51–63.

    CAS  Google Scholar 

  52. Weisinger RS, Considine P, Denton DA, McKinley MJ. Rapid effect of change in cerebrospinal fluid sodium concentration on salt appetite. Nature. 1979;280(5722):490–1.

    Article  CAS  PubMed  Google Scholar 

  53. Chiaraviglio E, Perez Guaita MF. The effect of intracerebroventricular hypertonic infusion on sodium appetite in rats after peritoneal dialysis. Physiol Behav. 1986;37(5):695–9.

    Article  CAS  PubMed  Google Scholar 

  54. Van Huysse JW, Amin MS, Yang B, Leenen FH. Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. Hypertension. 2012;60(3):691–6. doi:10.1161/HYPERTENSIONAHA.112.193045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Denton DA, McKinley MJ, Weisinger RS. Hypothalamic integration of body fluid regulation. Proc Natl Acad Sci U S A. 1996;93(14):7397–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. McKinley MJ, Denton DA, Weisinger RS. Sensors for antidiuresis and thirst—osmoreceptors or CSF sodium detectors? Brain Res. 1978;141(1):89–103.

    Article  CAS  PubMed  Google Scholar 

  57. Johnson RF, Beltz TG, Thunhorst RL, Johnson AK. Investigations on the physiological controls of water and saline intake in C57BL/6 mice. Am J Physiol Regul Integr Comp Physiol. 2003;285(2):R394–403. doi:10.1152/ajpregu.00130.2003.

    Article  CAS  PubMed  Google Scholar 

  58. Andersson B. Thirst--and brain control of water balance. Am Sci. 1971;59(4):408–15.

    CAS  PubMed  Google Scholar 

  59. Fitzsimons JT. Bengt Andersson's pioneering demonstration of the hypothalamic "drinking area" and the subsequent osmoreceptor/sodium receptor controversy. Acta Physiol Scand Suppl. 1989;583:15–25.

    CAS  PubMed  Google Scholar 

  60. Watanabe E, Fujikawa A, Matsunaga H, Yasoshima Y, Sako N, Yamamoto T, et al. Nav2/NaG channel is involved in control of salt-intake behavior in the CNS. J Neurosci. 2000;20(20):7743–51.

    CAS  PubMed  Google Scholar 

  61. Watanabe E, Hiyama TY, Shimizu H, Kodama R, Hayashi N, Miyata S, et al. Sodium-level-sensitive sodium channel Na(x) is expressed in glial laminate processes in the sensory circumventricular organs. Am J Physiol Regul Integr Comp Physiol. 2006;290(3):R568–76. doi:10.1152/ajpregu.00618.2005.

    Article  CAS  PubMed  Google Scholar 

  62. Hiyama TY, Watanabe E, Okado H, Noda M. The subfornical organ is the primary locus of sodium-level sensing by Na(x) sodium channels for the control of salt-intake behavior. J Neurosci. 2004;24(42):9276–81. doi:10.1523/JNEUROSCI.2795-04.2004.

    Article  CAS  PubMed  Google Scholar 

  63. Hiyama TY, Watanabe E, Ono K, Inenaga K, Tamkun MM, Yoshida S, et al. Na(x) channel involved in CNS sodium-level sensing. Nat Neurosci. 2002;5(6):511–2. doi:10.1038/nn856.

    Article  CAS  PubMed  Google Scholar 

  64. Noda M. The subfornical organ, a specialized sodium channel, and the sensing of sodium levels in the brain. Neuroscientist. 2006;12(1):80–91. doi:10.1177/1073858405279683.

    Article  CAS  PubMed  Google Scholar 

  65. Eriksson L. Negligible role of CSF cations other than Na+ in the central regulation of ADH release. Acta Physiol Scand. 1976;97(3):398–400. doi:10.1111/j.1748-1716.1976.tb10280.x.

    Article  CAS  PubMed  Google Scholar 

  66. Richter CP. Increased salt appetite in adrenalectomized rats. Am J Phys. 1936;115:155–61.

    CAS  Google Scholar 

  67. Richter CP, Eckert JF. Mineral metabolism of adrenalectomized rats studied by the appetite method. Endocrinology. 1938;22:214–24.

    Article  CAS  Google Scholar 

  68. Wilkins L, Richter CP. A great craving for salt by a child with cortico-adrenal insufficiency. J Am Med Assoc. 1940;114:866–8.

    Google Scholar 

  69. Ahima R, Krozowski Z, Harlan R. Type I corticosteroid receptor-like immunoreactivity in the rat CNS: distribution and regulation by corticosteroids. J Comp Neurol. 1991;313(3):522–38. doi:10.1002/cne.903130312.

    Article  CAS  PubMed  Google Scholar 

  70. Gomez-Sanchez EP, Gomez-Sanchez CM, Plonczynski M, Gomez-Sanchez CE. Aldosterone synthesis in the brain contributes to Dahl salt-sensitive rat hypertension. Exp Physiol. 2010;95(1):120–30. doi:10.1113/expphysiol.2009.048900.

    Article  CAS  PubMed  Google Scholar 

  71. Amin MS, Wang HW, Reza E, Whitman SC, Tuana BS, Leenen FH. Distribution of epithelial sodium channels and mineralocorticoid receptors in cardiovascular regulatory centers in rat brain. Am J Physiol Regul Integr Comp Physiol. 2005;289(6):R1787–97. doi:10.1152/ajpregu.00063.2005.

    Article  CAS  PubMed  Google Scholar 

  72. Formenti S, Bassi M, Nakamura NB, Schoorlemmer GH, Menani JV, Colombari E. Hindbrain mineralocorticoid mechanisms on sodium appetite. Am J Physiol Regul Integr Comp Physiol. 2013;304(3):R252–9. doi:10.1152/ajpregu.00385.2011.

    Article  CAS  PubMed  Google Scholar 

  73. Sakai RR, Nicolaidis S, Epstein AN. Salt appetite is suppressed by interference with angiotensin II and aldosterone. Am J Phys. 1986;251(4 Pt 2):R762–8.

    CAS  Google Scholar 

  74. Shade RE, Blair-West JR, Carey KD, Madden LJ, Weisinger RS, Denton DA. Synergy between angiotensin and aldosterone in evoking sodium appetite in baboons. Am J Physiol Regul Integr Comp Physiol. 2002;283(5):R1070–8. doi:10.1152/ajpregu.00248.2002.

    Article  CAS  PubMed  Google Scholar 

  75. Fluharty SJ, Epstein AN. Sodium appetite elicited by intracerebroventricular infusion of angiotensin II in the rat: II. Synergistic interaction with systemic mineralocorticoids. Behav Neurosci. 1983;97(5):746–58.

    Article  CAS  PubMed  Google Scholar 

  76. Epstein AN. Mineralocorticoids and cerebral angiotensin may act together to produce sodium appetite. Peptides. 1982;3(3):493–4.

    Article  CAS  PubMed  Google Scholar 

  77. Cupples WA, Braam B. Assessment of renal autoregulation. Am J Physiol Renal Physiol. 2007;292(4):F1105–23. doi:10.1152/ajprenal.00194.2006.

    Article  CAS  PubMed  Google Scholar 

  78. Mitchell KD, Braam B, Navar LG. Hypertensinogenic mechanisms mediated by renal actions of renin-angiotensin system. Hypertension. 1992;19(1 Suppl):I18–27.

    Article  CAS  PubMed  Google Scholar 

  79. Pontes RB, Girardi AC, Nishi EE, Campos RR, Bergamaschi CT. Crosstalk between the renal sympathetic nerve and intrarenal angiotensin II modulates proximal tubular sodium reabsorption. Exp Physiol. 2015;100(5):502–6. doi:10.1113/EP085075.

    Article  CAS  PubMed  Google Scholar 

  80. Saccomani G, Mitchell KD, Navar LG. Angiotensin II stimulation of Na(+)-H+ exchange in proximal tubule cells. Am J Phys. 1990;258(5 Pt 2):F1188–95.

    CAS  Google Scholar 

  81. Eiam-Ong S, Hilden SA, Johns CA, Madias NE. Stimulation of basolateral Na(+)-HCO3- cotransporter by angiotensin II in rabbit renal cortex. Am J Phys. 1993;265(2 Pt 2):F195–203.

    CAS  Google Scholar 

  82. Schiessl IM, Rosenauer A, Kattler V, Minuth WW, Oppermann M, Castrop H. Dietary salt intake modulates differential splicing of the Na-K-2Cl cotransporter NKCC2. Am J Physiol Renal Physiol. 2013;305(8):F1139–48. doi:10.1152/ajprenal.00259.2013.

    Article  CAS  PubMed  Google Scholar 

  83. Rojas-Vega L, Gamba G. Mini-review: regulation of the renal NaCl cotransporter by hormones. Am J Physiol Renal Physiol. 2016;310(1):F10–4. doi:10.1152/ajprenal.00354.2015.

    CAS  PubMed  Google Scholar 

  84. Verrey F. Transcriptional control of sodium transport in tight epithelial by adrenal steroids. J Membr Biol. 1995;144(2):93–110.

    Article  CAS  PubMed  Google Scholar 

  85. Garty H. Regulation of Na+ permeability by aldosterone. Semin Nephrol. 1992;12(1):24–9.

    CAS  PubMed  Google Scholar 

  86. Lau C, Sudbury I, Thomson M, Howard PL, Magil AB, Cupples WA. Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes. Am J Physiol Regul Integr Comp Physiol. 2009;296(6):R1761–70. doi:10.1152/ajpregu.90731.2008.

    Article  CAS  PubMed  Google Scholar 

  87. Sima CA, Koeners MP, Joles JA, Braam B, Magil AB, Cupples WA. Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake. Diabetologia. 2012;55(8):2246–55. doi:10.1007/s00125-012-2569-2.

    Article  CAS  PubMed  Google Scholar 

  88. Drueke TB, Muntzel M. Heterogeneity of blood pressure responses to salt restriction and salt appetite in rats. Klin Wochenschr. 1991;69(Suppl 25):73–8.

    PubMed  Google Scholar 

  89. • Koomans HA, Roos JC, Dorhout Mees EJ, Delawi IM. Sodium balance in renal failure. A comparison of patients with normal subjects under extremes of sodium intake. Hypertension. 1985;7(5):714–21. A small but convincing study on sodium sensitivity in normal subjects and subjects with CKD.

    Article  CAS  PubMed  Google Scholar 

  90. Essig M, Escoubet B, de Zuttere D, Blanchet F, Arnoult F, Dupuis E, et al. Cardiovascular remodelling and extracellular fluid excess in early stages of chronic kidney disease. Nephrol Dial Transplant. 2008;23(1):239–48. doi:10.1093/ndt/gfm542.

    Article  CAS  PubMed  Google Scholar 

  91. •• McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW, et al. A randomized trial of dietary sodium restriction in CKD. J Am Soc Nephrol. 2013;24(12):2096–103. doi:10.1681/ASN.2013030285. This is a unique translational study on sodium restriction on renal function and proteinuria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Koomans HA, Braam B, Geers AB, Roos JC, Dorhout Mees EJ. The importance of plasma protein for blood volume and blood pressure homeostasis. Kidney Int. 1986;30(5):730–5.

    Article  CAS  PubMed  Google Scholar 

  93. Wang DH, Du Y, Yao A, Hu Z. Regulation of type 1 angiotensin II receptor and its subtype gene expression in kidney by sodium loading and angiotensin II infusion. J Hypertens. 1996;14(12):1409–15.

    Article  CAS  PubMed  Google Scholar 

  94. Becker BN, Cheng HF, Burns KD, Harris RC. Polarized rabbit type 1 angiotensin II receptors manifest differential rates of endocytosis and recycling. Am J Phys. 1995;269(4 Pt 1):C1048–56.

    CAS  Google Scholar 

  95. Bellucci A, Wilkes BM. Mechanism of sodium modulation of glomerular angiotensin receptors in the rat. J Clin Invest. 1984;74(5):1593–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wang JM, Veerasingham SJ, Tan J, Leenen FH. Effects of high salt intake on brain AT1 receptor densities in Dahl rats. Am J Physiol Heart Circ Physiol. 2003;285(5):H1949–55.

    Article  CAS  PubMed  Google Scholar 

  97. Zheng W, Ji H, Szabo Z, Brown PR, Yoo SE, Sandberg K. Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation. Kidney Int. 2001;59(5):1881–90. doi:10.1046/j.1523-1755.2001.0590051881.x.

    Article  CAS  PubMed  Google Scholar 

  98. Nickenig G, Strehlow K, Roeling J, Zolk O, Knorr A, Bohm M. Salt induces vascular AT1 receptor overexpression in vitro and in vivo. Hypertension. 1998;31(6):1272–7.

    Article  CAS  PubMed  Google Scholar 

  99. Makita N, Iwai N, Inagami T, Badr KF. Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. Biochem Biophys Res Commun. 1992;185(1):142–6.

    Article  CAS  PubMed  Google Scholar 

  100. Nickenig G, Baumer AT, Temur Y, Kebben D, Jockenhovel F, Bohm M. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation. 1999;100(21):2131–4.

    Article  CAS  PubMed  Google Scholar 

  101. Nickenig G, Jung O, Strehlow K, Zolk O, Linz W, Scholkens BA, et al. Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression. Am J Phys. 1997;272(6 Pt 2):H2701–7.

    CAS  Google Scholar 

  102. Privratsky JR, Wold LE, Sowers JR, Quinn MT, Ren J. AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT1 receptor and NADPH oxidase. Hypertension. 2003;42(2):206–12.

    Article  CAS  PubMed  Google Scholar 

  103. Sodhi CP, Kanwar YS, Sahai A. Hypoxia and high glucose upregulate AT1 receptor expression and potentiate ANG II-induced proliferation in VSM cells. Am J Physiol Heart Circ Physiol. 2003;284(3):H846–52.

    Article  CAS  PubMed  Google Scholar 

  104. Dorffel Y, Latsch C, Stuhlmuller B, Schreiber S, Scholze S, Burmester GR, et al. Preactivated peripheral blood monocytes in patients with essential hypertension. Hypertension. 1999;34(1):113–7.

    Article  CAS  PubMed  Google Scholar 

  105. Dorffel Y, Franz S, Pruss A, Neumann G, Rohde W, Burmester GR, et al. Preactivated monocytes from hypertensive patients as a factor for atherosclerosis? Atherosclerosis. 2001;157(1):151–60.

    Article  CAS  PubMed  Google Scholar 

  106. Syrbe U, Moebes A, Scholze J, Swidsinski A, Dorffel Y. Effects of the angiotensin II type 1 receptor antagonist telmisartan on monocyte adhesion and activation in patients with essential hypertension. Hypertens Res. 2007;30(6):521–8. doi:10.1291/hypres.30.521.

    Article  CAS  PubMed  Google Scholar 

  107. Wesseling S, Ishola DA Jr, Joles JA, Bluyssen HA, Koomans HA, Braam B. Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor. Am J Physiol Renal Physiol. 2005;288(6):F1191–200. doi:10.1152/ajprenal.00322.2004.

    Article  CAS  PubMed  Google Scholar 

  108. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension. 1997;30(5):1238–46.

    Article  CAS  PubMed  Google Scholar 

  109. Suzuki H, Yamamoto T, Ikegaya N, Hishida A. Dietary salt intake modulates progression of antithymocyte serum nephritis through alteration of glomerular angiotensin II receptor expression. Am J Physiol Renal Physiol. 2004;286(2):F267–77. doi:10.1152/ajprenal.00059.2003.

    Article  CAS  PubMed  Google Scholar 

  110. Widdop RE, Matrougui K, Levy BI, Henrion D. AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension. 2002;40(4):516–20.

    Article  CAS  PubMed  Google Scholar 

  111. Bonnet F, Cooper ME, Carey RM, Casley D, Cao Z. Vascular expression of angiotensin type 2 receptor in the adult rat: influence of angiotensin II infusion. J Hypertens. 2001;19(6):1075–81.

    Article  CAS  PubMed  Google Scholar 

  112. Wang ZQ, Millatt LJ, Heiderstadt NT, Siragy HM, Johns RA, Carey RM. Differential regulation of renal angiotensin subtype AT1A and AT2 receptor protein in rats with angiotensin-dependent hypertension. Hypertension. 1999;33(1):96–101.

    Article  CAS  PubMed  Google Scholar 

  113. Ruiz-Ortega M, Lorenzo O, Ruperez M, Suzuki Y, Egido J. Angiotensin II activates nuclear transcription factor-kappaB in aorta of normal rats and in vascular smooth muscle cells of AT1 knockout mice. Nephrol Dial Transplant. 2001;16(Suppl 1):27–33.

    Article  CAS  PubMed  Google Scholar 

  114. Wolf G, Wenzel U, Burns KD, Harris RC, Stahl RA, Thaiss F. Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors. Kidney Int. 2002;61(6):1986–95. doi:10.1046/j.1523-1755.2002.00365.x.

    Article  CAS  PubMed  Google Scholar 

  115. Okada H, Watanabe Y, Kobayashi T, Kikuta T, Kanno Y, Suzuki H. Angiotensin II type 1 and type 2 receptors reciprocally modulate pro-inflammatory/ pro-fibrotic reactions in activated splenic lymphocytes. Am J Nephrol. 2004;24(3):322–9. doi:10.1159/000078496.

    Article  CAS  PubMed  Google Scholar 

  116. Nakamura S, Averill DB, Chappell MC, Diz DI, Brosnihan KB, Ferrario CM. Angiotensin receptors contribute to blood pressure homeostasis in salt-depleted SHR. Am J Physiol Regul Integr Comp Physiol. 2003;284(1):R164–73. doi:10.1152/ajpregu.00210.2002.

    Article  CAS  PubMed  Google Scholar 

  117. Iyer SN, Averill DB, Chappell MC, Yamada K, Allred AJ, Ferrario CM. Contribution of angiotensin-(1-7) to blood pressure regulation in salt-depleted hypertensive rats. Hypertension. 2000;36(3):417–22.

    Article  CAS  PubMed  Google Scholar 

  118. Sullivan JC, Bhatia K, Yamamoto T, Elmarakby AA. Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats. Hypertension. 2010;56(4):658–66. doi:10.1161/HYPERTENSIONAHA.110.153668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Zimmerman MA, Baban B, Tipton AJ, O'Connor PM, Sullivan JC. Chronic ANG II infusion induces sex-specific increases in renal T cells in Sprague-Dawley rats. Am J Physiol Renal Physiol. 2015;308(7):F706–12. doi:10.1152/ajprenal.00446.2014.

    Article  CAS  PubMed  Google Scholar 

  120. Singh I, Grams M, Wang WH, Yang T, Killen P, Smart A, et al. Coordinate regulation of renal expression of nitric oxide synthase, renin, and angiotensinogen mRNA by dietary salt. Am J Phys. 1996;270(6 Pt 2):F1027–37.

    CAS  Google Scholar 

  121. Ying WZ, Sanders PW. Dietary salt enhances glomerular endothelial nitric oxide synthase through TGF-beta1. Am J Phys. 1998;275(1 Pt 2):F18–24.

    CAS  Google Scholar 

  122. Hennington BS, Zhang H, Miller MT, Granger JP, Reckelhoff JF. Angiotensin II stimulates synthesis of endothelial nitric oxide synthase. Hypertension. 1998;31(1 Pt 2):283–8.

    Article  CAS  PubMed  Google Scholar 

  123. Zhang J, Patel MB, Griffiths R, Mao A, Song YS, Karlovich NS, et al. Tumor necrosis factor-alpha produced in the kidney contributes to angiotensin II-dependent hypertension. Hypertension. 2014;64(6):1275–81. doi:10.1161/HYPERTENSIONAHA.114.03863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Crowley SD, Song YS, Lin EE, Griffiths R, Kim HS, Ruiz P. Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2010;298(4):R1089–97. doi:10.1152/ajpregu.00373.2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kielstein JT, Boger RH, Bode-Boger SM, Frolich JC, Haller H, Ritz E, et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol. 2002;13(1):170–6.

    CAS  PubMed  Google Scholar 

  126. Ni Z, Vaziri ND. Effect of salt loading on nitric oxide synthase expression in normotensive rats. Am J Hypertens. 2001;14(2):155–63.

    Article  CAS  PubMed  Google Scholar 

  127. Boegehold MA. Flow-dependent arteriolar dilation in normotensive rats fed low- or high-salt diets. Am J Phys. 1995;269(4 Pt 2):H1407–14.

    CAS  Google Scholar 

  128. Li X, Xing W, Wang Y, Mi C, Zhang Z, Ma H, et al. Upregulation of caveolin-1 contributes to aggravated high-salt diet-induced endothelial dysfunction and hypertension in type 1 diabetic rats. Life Sci. 2014;113(1–2):31–9. doi:10.1016/j.lfs.2014.07.027.

    Article  CAS  PubMed  Google Scholar 

  129. Nurkiewicz TR, Wu G, Li P, Boegehold MA. Decreased arteriolar tetrahydrobiopterin is linked to superoxide generation from nitric oxide synthase in mice fed high salt. Microcirculation. 2010;17(2):147–57. doi:10.1111/j.1549-8719.2009.00014.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dickinson KM, Keogh JB, Clifton PM. Effects of a low-salt diet on flow-mediated dilatation in humans. Am J Clin Nutr. 2009;89(2):485–90. doi:10.3945/ajcn.2008.26856.

    Article  CAS  PubMed  Google Scholar 

  131. Ying WZ, Sanders PW. Dietary salt increases endothelial nitric oxide synthase and TGF-beta1 in rat aortic endothelium. Am J Phys. 1999;277(4 Pt 2):H1293–8.

    CAS  Google Scholar 

  132. Shultz PJ, Tolins JP. Adaptation to increased dietary salt intake in the rat. Role of endogenous nitric oxide. J Clin Invest. 1993;91(2):642–50. doi:10.1172/JCI116244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Bech JN, Nielsen CB, Ivarsen P, Jensen KT, Pedersen EB. Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans. Am J Phys. 1998;274(5 Pt 2):F914–23.

    CAS  Google Scholar 

  134. van Hinsbergh VW. Endothelium—role in regulation of coagulation and inflammation. Semin Immunopathol. 2012;34(1):93–106. doi:10.1007/s00281-011-0285-5.

    Article  PubMed  CAS  Google Scholar 

  135. Kusche-Vihrog K, Callies C, Fels J, Oberleithner H. The epithelial sodium channel (ENaC): mediator of the aldosterone response in the vascular endothelium? Steroids. 2010;75(8–9):544–9. doi:10.1016/j.steroids.2009.09.003.

    Article  CAS  PubMed  Google Scholar 

  136. Oberleithner H, Riethmuller C, Schillers H, MacGregor GA, de Wardener HE, Hausberg M. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci U S A. 2007;104(41):16281–6. doi:10.1073/pnas.0707791104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Halterman JA, Kwon HM, Zargham R, Bortz PD, Wamhoff BR. Nuclear factor of activated T cells 5 regulates vascular smooth muscle cell phenotypic modulation. Arterioscler Thromb Vasc Biol. 2011;31(10):2287–96. doi:10.1161/ATVBAHA.111.232165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. DiBona GF, Sawin LL. Renal nerve activity in conscious rats during volume expansion and depletion. Am J Phys. 1985;248(1 Pt 2):F15–23.

    CAS  Google Scholar 

  139. DiBona GF, Jones SY, Sawin LL. Effect of endogenous angiotensin II on renal nerve activity and its arterial baroreflex regulation. Am J Phys. 1996;271(2 Pt 2):R361–7.

    CAS  Google Scholar 

  140. DiBona GF, Jones SY. Effect of dietary sodium intake on the responses to bicuculline in the paraventricular nucleus of rats. Hypertension. 2001;38(2):192–7.

    Article  CAS  PubMed  Google Scholar 

  141. Abboud FM. Effects of sodium, angiotensin, and steroids on vascular reactivity in man. Fed Proc. 1974;33(2):143–9.

    CAS  PubMed  Google Scholar 

  142. Kunze DL, Brown AM. Sodium sensitivity of baroreceptors. Reflex effects on blood pressure and fluid volume in the cat. Circ Res. 1978;42(5):714–20.

    Article  CAS  PubMed  Google Scholar 

  143. Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension. 1989;14(2):177–83.

    Article  CAS  PubMed  Google Scholar 

  144. Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Bolla G, Mancia G. Baroreflex impairment by low sodium diet in mild or moderate essential hypertension. Hypertension. 1997;29(3):802–7.

    Article  CAS  PubMed  Google Scholar 

  145. • Ligtenberg G, Blankestijn PJ, Oey PL, Klein IH, Dijkhorst-Oei LT, Boomsma F, et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med. 1999;340(17):1321–8. doi:10.1056/NEJM199904293401704. Study in humans with CKD demonstrating the role of the renin-angiotenisn system in baroreceptor control.

    Article  CAS  PubMed  Google Scholar 

  146. Barajas L, Liu L, Powers K. Anatomy of the renal innervation: intrarenal aspects and ganglia of origin. Can J Physiol Pharmacol. 1992;70(5):735–49.

    Article  CAS  PubMed  Google Scholar 

  147. Klinger F, Grimm R, Steinbach A, Tanneberger M, Kunert-Keil C, Rettig R, et al. Low NaCl intake elevates renal medullary endothelin-1 and endothelin A (ETA) receptor mRNA but not the sensitivity of renal Na+ excretion to ETA receptor blockade in rats. Acta Physiol (Oxf). 2008;192(3):429–42. doi:10.1111/j.1748-1716.2007.01751.x.

    Article  CAS  Google Scholar 

  148. Kopp UC, Grisk O, Cicha MZ, Smith LA, Steinbach A, Schluter T, et al. Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin. Am J Physiol Regul Integr Comp Physiol. 2009;297(2):R337–51. doi:10.1152/ajpregu.91029.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Mecawi AS, Vilhena-Franco T, Fonseca FV, Reis LC, Elias LL, Antunes-Rodrigues J. The role of angiotensin II on sodium appetite after a low-sodium diet. J Neuroendocrinol. 2013;25(3):281–91. doi:10.1111/j.1365-2826.2012.02388.x.

    Article  CAS  PubMed  Google Scholar 

  150. Lu B, Yang XJ, Chen K, Yang DJ, Yan JQ. Dietary sodium deprivation evokes activation of brain regional neurons and down-regulation of angiotensin II type 1 receptor and angiotensin-convertion enzyme mRNA expression. Neuroscience. 2009;164(3):1303–11. doi:10.1016/j.neuroscience.2009.08.064.

    Article  CAS  PubMed  Google Scholar 

  151. Stricker EM, Thiels E, Verbalis JG. Sodium appetite in rats after prolonged dietary sodium deprivation: a sexually dimorphic phenomenon. Am J Phys. 1991;260(6 Pt 2):R1082–8.

    CAS  Google Scholar 

  152. DiBona GF, Jones SY. Sodium intake influences hemodynamic and neural responses to angiotensin receptor blockade in rostral ventrolateral medulla. Hypertension. 2001;37(4):1114–23.

    Article  CAS  PubMed  Google Scholar 

  153. Luft FC, Rankin LI, Henry DP, Bloch R, Grim CE, Weyman AE, et al. Plasma and urinary norepinephrine values at extremes of sodium intake in normal man. Hypertension. 1979;1(3):261–6.

    Article  CAS  PubMed  Google Scholar 

  154. Warren SE, Vieweg WV, O'Connor DT. Sympathetic nervous system activity during sodium restriction in essential hypertension. Clin Cardiol. 1980;3(5):348–51.

    Article  CAS  PubMed  Google Scholar 

  155. Timio M, Venanzi S, Lolli S, Lippi G, Verdura C, Monarca C, et al. "non-dipper" hypertensive patients and progressive renal insufficiency: a 3-year longitudinal study. Clin Nephrol. 1995;43(6):382–7.

    CAS  PubMed  Google Scholar 

  156. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. 1994;24(6):793–801.

    Article  CAS  PubMed  Google Scholar 

  157. Menaker M. Circadian rhythms. Circadian Photoreception Sci. 2003;299(5604):213–4. doi:10.1126/science.1081112.

    CAS  Google Scholar 

  158. Azar S, Ernsberger P, Livingston S, Azar P, Iwai J. Paraventricular-suprachiasmatic lesions prevent salt-induced hypertension in Dahl rats. Clin Sci (Lond). 1981;61 Suppl 7:49s–51s.

  159. Fujii T, Uzu T, Nishimura M, Takeji M, Kuroda S, Nakamura S, et al. Circadian rhythm of natriuresis is disturbed in nondipper type of essential hypertension. Am J Kidney Dis. 1999;33(1):29–35.

    Article  CAS  PubMed  Google Scholar 

  160. Damasceno A, Caupers P, Santos A, Lobo E, Sevene E, Bicho M, et al. Influence of salt intake on the daytime-nighttime blood pressure variation in normotensive and hypertensive black subjects. Rev Port Cardiol. 2000;19(3):315–29.

    CAS  PubMed  Google Scholar 

  161. Combe R, Mudgett J, El Fertak L, Champy MF, Ayme-Dietrich E, Petit-Demouliere B, et al. How does circadian rhythm impact salt sensitivity of blood pressure in mice? A study in two close C57Bl/6 Substrains. PLoS One. 2016;11(4):e0153472. doi:10.1371/journal.pone.0153472.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Pati P, Fulton DJ, Bagi Z, Chen F, Wang Y, Kitchens J, et al. Low-salt diet and circadian dysfunction synergize to induce angiotensin II-dependent hypertension in mice. Hypertension. 2016;67(3):661–8. doi:10.1161/HYPERTENSIONAHA.115.06194.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Russcher M, Koch B, Nagtegaal E, van der Putten K, ter Wee P, Gaillard C. The role of melatonin treatment in chronic kidney disease. Front Biosci (Landmark Ed). 2012;17:2644–56.

    Article  CAS  Google Scholar 

  164. Koch BC, Nagtegaal JE, Kerkhof GA, ter Wee PM. Circadian sleep-wake rhythm disturbances in end-stage renal disease. Nat Rev Nephrol. 2009;5(7):407–16. doi:10.1038/nrneph.2009.88.

    Article  PubMed  Google Scholar 

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Acknowledgements

BB is supported by the Kidney Health Translational Research Chair, awarded by the Fac. Medicine and Dentistry / Dept. Medicine, Div. Nephrology, University of Alberta and by a Grant-in-Aid by the Heart and Stroke Foundation of Canada. XH is supported by the Li Ka-Shing Foundation.

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Authors and Affiliations

  1. Department of Medicine, University of Alberta, Edmonton, AB, Canada

    Branko Braam, Xiaohua Huang & Shereen M. Hamza

  2. Department of Physiology, University of Alberta, Edmonton, AB, Canada

    Branko Braam & Shereen M. Hamza

  3. Department of Medicine / Division of Nephrology and Immunology, University of Alberta Hospital, 11-132 CSB Clinical Sciences Building, Edmonton, AB, T6G 2G3, Canada

    Branko Braam

  4. Biomedical Physiology & Kinesiology, Simon Fraser University, Burnaby, BC, Canada

    William A. Cupples

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Dr. Braam is supported by the Kidney Health Translational Research Chair and by a Grant-in-aid by the Heart and Heart and Stroke Foundation of Canada. Xiaohua Huang is supported by the Li Ka-Shing Foundation. Drs. Cupples and Hamza declare no conflicts of interest relevant to this manuscript.

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Braam, B., Huang, X., Cupples, W.A. et al. Understanding the Two Faces of Low-Salt Intake. Curr Hypertens Rep 19, 49 (2017). https://doi.org/10.1007/s11906-017-0744-z

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