Hypertension Journal

Register      Login

VOLUME 3 , ISSUE 4 ( 2017 ) > List of Articles


Salt Sensitivity and Hypertension

Anuj Maheshwari, Harish Basera

Keywords : Dietary salt, Hypertension, Salt sensitivity

Citation Information : Maheshwari A, Basera H. Salt Sensitivity and Hypertension. Hypertens J 2017; 3 (4):178-182.

DOI: 10.5005/jp-journals-10043-0092

License: CC BY-ND 4.0

Published Online: 01-04-2018

Copyright Statement:  Copyright © 2017; The Author(s).


Enough evidence is there to link excess salt intake with cardiovascular and renal risks through hypertension though substantial evidence is also there to support that blood pressure is not always responding to salt. A lot of metabolic and neurohormonal factors determine this salt sensitivity in addition to genetic factors that determine substantial excretion of salt, so it may not increase blood pressure despite high intake. Salt-sensitive hypertensives have reduced levels of urinary endothelin, contributing to impaired natriuresis in response to a salt load. Salt load also increases free radicals and paradoxically decreases excretion of nitric oxide metabolites in salt-sensitive individuals. Type 2 diabetic patients with microalbuminuria are more salt sensitive as they have lower urinary excretion of nitric oxide. Nitric oxide deficiency facilitates endothelial dysfunction causing hypertension in salt-sensitive people, impeding vasodilation after salt load. Sympathetic nervous system plays a significant role in maintenance of blood pressure in response to salt through urinary and plasma levels of catecholamine and renal nerve activity. Apart from this, atrial natriuretic peptides (ANPs) and cytochrome P450-derived metabolites of arachidonic acid play significant roles. Insomnia and menopause increase salt sensitivity. Kidney provides sensitive and specific biomarkers for salt sensitivity in the form of proteomics, and renal proximal tubule cells, microribonucleic acid (miRNA), and exosomes are excreted into the urine apart from genetic biomarkers. A J-shaped curve relationship exists between salt intake and mortality. Salt intakes above and below the range of 2.5 to 6.0 gm/day are associated with high cardiovascular risk. Salt restriction can be a cause of hypertension in inverse salt-sensitive people. Available prevalence studies do not differentiate between salt-sensitive and salt-resistant populations, nor do they include normotensive salt-sensitive people who get their blood pressure raised in response to dietary salt. In these circumstances, salt sensitivity arises as an independent risk factor for cardiovascular mortality and morbidity. How to cite this article Maheshwari A, Basera H. Salt Sensitivity and Hypertension. Hypertens J 2017;3(4):178-182.

PDF Share
  1. Ambard L, Beaujard E. Causes de l'hypertension artérielle. Arch Gen Med 1904;1:520-533.
  2. Kempner W. Treatment of hypertensive vascular disease with the rice diet. Am J Med 1948 Apr;4(4):545-577.
  3. Ball CO, Meneely GR. Observations on dietary sodium chloride. J Am Diet Assoc 1957 Apr;33(4):366-370.
  4. Dahl LK, Heine M, Tassinari L. Effects of chronic salt ingestion. Evidence that genetic factors play an important role in susceptibility to experimental hypertension. J Exp Med 1962 Jun;115(6):1173-1190.
  5. Denton D, Weisinger R, Mundy NI, Wickings EJ, Dixson A, Moisson P, Pingard AM, Shade R, Carey D, Ardaillou R, et al. The effect of increased salt intake on blood pressure of chimpanzees. Nat Med 1995 Oct;1(10):1009-1016.
  6. 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 Jul;297(6644):319-328.
  7. The Trials of Hypertension Prevention Collaborative Research Group. 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 Mar;267(9):1213-1220.
  8. 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 Mar;157(6):657-667.
  9. Choi HY, Park HC, Ha SK. Salt sensitivity and hypertension: a paradigm shift from kidney malfunction to endothelial dysfunction. Electrolyte Blood Press 2015 Jun;13(1):7-16.
  10. Majid DS, Prieto MC, Navar LG. Salt sensitivity hypertension: perspective of intrarenal mechanism. Curr Hypertens Rev 2015;11(1):38-48.
  11. Guyton, AC.; Coleman, TG. Long-term regulation of the circulation: inter-relationship with body fluid volumes. In: Reeve E, Guyton AC, editors. Physical basis of circulatory transport: regulation and exchange. Philadelphia (PA): Saunders; 1967. pp. 179-201.
  12. Cowley AW Jr. Long-term control of arterial blood pressure. Physiol Rev 1992 Jan;72(1):23l-300.
  13. Lifton R, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell 2001 Feb;104(4):545-556.
  14. Cappuccio FP, Markandu ND, Sagnella GA, MacGregor GA. Sodium restriction lowers high blood pressure through a decreased response of the renin system: direct evidence using saralasin. J Hypertens 1985 Jun;3(3):243-247.
  15. He FJ, Markandu ND, Sagnella GA, MacGregor GA. Importance of the renin system in determining blood pressure fall with salt restriction in black and white hypertensives. Hypertension 1998 Nov;32(5):820-824.
  16. Williams GH, Dluhy RG, Lifton RP, Moore TJ, Gleason R, Williams R, Hunt SC, Hopkins PN, Hollenberg NK. Non-modulation as an intermediate phenotype in essential hypertension. Hypertension 1992 Dec;20(6):788-796.
  17. Hoffman A, Grossman E, Goldstein DS, Gill JR Jr, Keiser HR. Urinary excretion rate of endothelin-1 in patients with essential hypertension and salt sensitivity. Kidney Int 1994 Feb;45(2):556-560.
  18. Imanishi M, Okada N, Konishi Y, Morikawa T, Maeda I, Kitabayashi C, Masada M, Shirahashi N, Wilcox CS, Nishiyama A. Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy. J Renin-Angiotensin-Aldosterone Syst 2012 Aug;14(1):67-73.
  19. Campese VM, Amar M, Anjali C, Medhat T, Wurgaft A. Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension. J Hum Hypertens 1997 Aug;11(8):527-532.
  20. Chen YF, Meng QC, Wyss JM, Jin H, Oparil S. High NaCl diet reduces hypothalamic norepinephrine turnover in hypertensive rats. Hypertension 1988 Jan;11(1):55-62.
  21. Oparil S, Yang RH, Jin HK, Wyss JM, Chen YF. Central mechanisms of hypertension. Am J Hypertens 1989 Jun;2(6 Pt 1):477-485.
  22. Campese VM, Romoff MS, Levitan D, Saglikes Y, Friedler RM, Massry SG. Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int 1982 Feb;21(2):371-378.
  23. Elijovich F, Laffer CL, Amador E, Gavras H, Bresnahan MR, Schiffrin EL. Regulation of plasma endothelin by salt in salt-sensitive hypertension. Circulation 2001 Jan;103(2):263-268.
  24. Zimmermann-Viehoff F, Weber CS, Merswolken M, Rudat M, Deter HC. Low anxiety males display higher degree of salt sensitivity, increased autonomic reactivity, and higher defensiveness. Am J Hypertens 2008 Dec;21(12):1292-1297.
  25. Lieb W, Pencina MJ, Jacques PF, Wang TJ, Larson MG, Levy D, Kannel WB, Vasan RS. Higher aldosterone and lower N-terminal proatrial natriuretic peptide as biomarkers of salt sensitivity in the community. Eur J Cardiovasc Prev Rehabil 2011 Aug;18(4):664-673.
  26. Melander O, von Wowern F, Frandsen E, Burri P, Willsteen G, Aurell M, Hulthen UL. Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma. J Hypertens 2007 Mar;25(3):619-627.
  27. Laffer CL, Laniado-Schwartzman M, Wang MH, Nasjletti A, Elijovich F. Differential regulation of natriuresis by 20-hydroxyeicosatetraenoic acid in human salt-sensitive versus salt-resistant hypertension. Circulation 2003 Feb;107(4):574-578.
  28. Felder RA, White MJ, Williams SM, Jose PA. Diagnostic tools for hypertension and salt sensitivity testing. Curr Opin Nephrol Hypertens 2013 Jan;22(1):65-76.
  29. Sullivan JM. Salt sensitivity. Definition, conception, methodology, and long-term issues. Hypertension 1991 Jan;17(1 Suppl):I61-I68.
  30. de la Sierra A, Giner V, Bragulat E, Coca A. Lack of correlation between two methods for the assessment of salt sensitivity in essential hypertension. J Hum Hypertens 2002 Apr;16(4):255-260.
  31. Yatabe MS, Yatabe J, Yoneda M, Watanabe T, Otsuki M, Felder RA, Jose PA, Sanada H. Salt sensitivity is associated with insulin resistance, sympathetic overactivity, and decreased suppression of circulating renin activity in lean patients with essential hypertension. Am J Clin Nutr 2010 Jul;92(1):77-82.
  32. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension 2001 Feb;37(2 Pt 2):429-432.
  33. Simonetti GD, Farese S, Aregger F, Uehlinger D, Frey FJ, Mohaupt MG. Nocturnal dipping behaviour in normotensive white children and young adults in response to changes in salt intake. J Hypertens 2010 May;28(5):1027-1033.
  34. Barton M, Meyer MR. Postmenopausal hypertension mechanisms and therapy. Hypertension 2009 Jul;54(1):11-18.
  35. Fisher ND, Hurwitz S, Jeunemaitre X, Hopkins PN, Hollenberg NK, Williams GH. Familial aggregation of low-renin hypertension. Hypertension 2002 Apr;39:914-918.
  36. Sanada H, Yatabe J, Midorikawa S, Hashimoto S, Watanabe T, Moore JH, Ritchie MD, Williams SM, Pezzullo JC, Sasaki M, et al. Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension. Clin Chem 2006 Mar;52(3):352-360.
  37. Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits. Science 2002 Dec;298(5602):2345-2349.
  38. Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA. Urinary exosome miRNome analysis and its application to salt sensitivity of blood pressure. Clin Biochem 2013 Aug;46(12):1131-1134.
  39. Esteva-Font C, Wang X, Ars E, Guillén-Gómez E, Sans L, González Saavedra I, Torres F, Torra R, Masilamani S, Ballarín JA, et al. Are sodium transporters in urinary exosomes reliable markers of tubular sodium reabsorption in hypertensive patients? Nephron Physiol 2010 Feb;114(3):25-34.
  40. Centers for Disease Control and Prevention (CDC). Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003-2010. MMWR Morb Mortal Wkly Rep 2012 Sep;61:703-709.
  41. Dorresteijn JA, van der Graaf Y, Spiering W, Grobbee DE, Bots ML, Visseren FL; Secondary Manifestations of Arterial Disease Study Group. Relation between blood pressure and vascular events and mortality in patients with manifest vascular disease: J-curve revisited. Hypertension 2012 Jan;59(1):14-21.
  42. de Wardener HE, MacGregor GA. Harmful effects of dietary salt in addition to hypertension. J Hum Hypertens 2002 Apr;16(4):213-223.
  43. Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database Syst Rev 2011 Jul;7:CD009217.
  44. Tihtonen KM, Kööbi T, Uotila JT. Arterial stiffness in preeclamptic and chronic hypertensive pregnancies. Eur J Obstet Gynecol Reprod Biol 2006 Sep-Oct;128(1-2):180-186.
  45. Rönnback M, Lampinen K, Groop PH, Kaaja R. Pulse wave reflection in currently and previously preeclamptic women. Hypertens Pregnancy 2005;24:171-180.
  46. Spasojevic M, Smith SA, Morris JM, Gallery ED. Peripheral arterial pulse wave analysis in women with pre-eclampsia and gestational hypertension. BJOG 2005 Nov;112(11):1475-1478.
  47. Elvan-Taşpinar A, Franx A, Bots ML, Bruinse HW, Koomans HA. Central hemodynamics of hypertensive disorders in pregnancy. Am J Hypertens 2004 Oct;17(10):941-946.
  48. Kaihura C, Savvidou MD, Anderson JM, McEniery CM, Nicolaides KH. Maternal arterial stiffness in pregnancies affected by preeclampsia. Am J Physiol Heart Circ Physiol 2009 Aug;297(2):H759-H764.
  49. Robb AO, Mills NL, Din JN, Smith IB, Paterson F, Newby DE, Denison FC. Influence of the menstrual cycle, pregnancy, and preeclampsia on arterial stiffness. Hypertension 2009 Jun;53(6):952-958.
  50. Avni B, Frenkel G, Shahar L, Golik A, Sherman D, Dishy V. Aortic stiffness in normal and hypertensive pregnancy. Blood Press 2010 Feb;19(1):11-15.
  51. Khalil A, Akolekar R, Syngelaki A, Elkhouli M, Nicolaides KH. Maternal hemodynamics at 11–13 weeks’ gestation and risk of pre-eclampsia. Ultrasound Obstet Gynecol 2012 Jul;40(1):28-34.
  52. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992 Feb;304(6824):405-412.
  53. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002 Mar;359(9311):995-1003.
  54. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trials-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005 Sep;366(9489):895-906.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.