High sodium causes hypertension: Evidence from clinical trials and animal experiments

doi:10.1016/S2095-4964(15)60155-8

Abstract

Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension.

Key words: High salt, Hypertension, Clinical trial, Models, Animal, Reviews

Vamsi Reddy, Arvind Sridhar, Roberto F. Machado, Jiwang Chen. High sodium causes hypertension: Evidence from clinical trials and animal experiments. Journal of Integrative Medicine, 2015, 13(1): 1-8.

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[1]	World Health Organization. A global brief on hypertension. Geneva: WHO Press, 2013: 1-40
[2]	Zhao D, Qi Y, Zheng Z, Wang Y, Zhang XY, Li HJ, Liu HH, Zhang XT, Du J, Liu J . Dietary factors associated with hypertension. Nat Rev Cardiol, 2011,8(8):456-465 doi: 10.1038/nrcardio.2011.75 pmid: 21727918
[3]	Neal B . Dietary salt is a public health hazard that requires vigorous attack. Can J Cardiol, 2014,30(5):502-506 doi: 10.1016/j.cjca.2014.02.005 pmid: 24786439
[4]	Tibazarwa KB, Damasceno AA . Hypertension in developing countries. Can J Cardiol, 2014,30(5):527-533 doi: 10.1016/j.cjca.2014.02.020
[5]	Van Vliet BN, Campbell NR ; Canadian Hypertension Education Program. Efforts to reduce sodium intake in Canada: why, what, and when? Can[J] Cardiol. 2011; 27(4):437-445.
[6]	Mozaffarian D, Fahimi S, Singh GM, Micha R, Khatibzadeh S, Engell RE, Lim S, Danaei G, Ezzati M, Powles J ; Global Burden of Diseases Nutrition and Chronic Diseases Expert Group.Global sodium consumption and death from cardiovascular causes. N Engl J Med, 2014,371(7):624-634 doi: 10.1016/j.jvs.2014.12.031 pmid: 25119608
[7]	DiNicolantonio JJ, Niazi AK, Sadaf R, O'Keefe JH, Lucan SC, Lavie CJ . Dietary sodium restriction: take it with a grain of salt. Am J Med, 2013,126(11):951-955 doi: 10.1016/j.amjmed.2013.05.020 pmid: 24054177
[8]	Mente A, O'Donnell MJ, Yusuf S . The population risks of dietary salt excess are exaggerated. Can J Cardiol, 2014,30(5):507-512 doi: 10.1016/j.cjca.2014.02.003 pmid: 24786440
[9]	Hoffmann IS, Alfieri AB, Cubeddu LX . Salt-resistant and salt-sensitive phenotypes determine the sensitivity of blood pressure to weight loss in overweight/obese patients. J Clin Hypertens (Greenwich), 2008,10(5):355-361 doi: 10.1111/j.1751-7176.2008.07609.x
[10]	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, 2010,92(1):77-82 doi: 10.3945/ajcn.2009.29028
[11]	Kayima J, Wanyenze RK, Katamba A, Leontsini E, Nuwaha F . Hypertension awareness, treatment and control in Africa: a systematic review. BMC Cardiovasc Disord, 2013,13:54 doi: 10.1186/1471-2261-13-54 pmid: 23915151
[12]	Dasgupta K, Quinn RR, Zarnke KB, Rabi DM, Ravani P, Daskalopoulou SS, Rabkin SW, Trudeau L, Feldman RD, Cloutier L, Prebtani A, Herman RJ, Bacon SL, Gilbert RE, Ruzicka M, McKay DW, Campbell TS, Grover S, Honos G, Schiffrin EL, Bolli P, Wilson TW, Lindsay P, Hill MD, Coutts SB, Gubitz G, Gelfer M, Vallée M, Prasad GV, Lebel M, McLean D, Arnold JM, Moe GW, Howlett JG, Boulanger JM, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Burns KD, Petrella RJ, Hiremath S, Milot A, Stone JA, Drouin D, Lavoie KL, Lamarre-Cliche M, Tremblay G, Hamet P, Fodor G, Carruthers SG, Pylypchuk GB, Burgess E, Lewanczuk R, Dresser GK, Penner SB, Hegele RA, McFarlane PA, Khara M, Pipe A, Oh P, Selby P, Sharma M, Reid DJ, Tobe SW, Padwal RS, Poirier L ; Canadian Hypertension Education Program.The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol, 2014,30(5):485-501 doi: 10.1016/j.cjca.2014.02.002
[13]	Islam AK, Majumder AA . Hypertension in Bangladesh: a review. Indian Heart J, 2012,64(3):319-323 doi: 10.1016/S0019-4832(12)60096-0 pmid: 22664819
[14]	Bi Z, Liang X, Xu A, Wang L, Shi X, Zhao W, Ma J, Guo X, Zhang X, Zhang J, Ren J, Yan L, Lu Z, Wang H, Tang J, Cai X, Dong J, Zhang J, Chu J, Engelgau M, Yang Q, Hong Y, Wang Y . Hypertension prevalence, awareness, treatment, and control and sodium intake in Shandong Province, China: baseline results from Shandong-Ministry of Health Action on Salt Reduction and Hypertension(SMASH), 2011. Prev Chronic Dis, 2014,11:E88
[15]	Addo J, Agyemang C, Smeeth L, de-Graft Aikins A, Edusei AK, Ogedegbe O . A review of population-based studies on hypertension in Ghana. Ghana Med J, 2012,46(2 Suppl):4-11 pmid: 23661811
[16]	Miura K . Epidemiology and prevention of hypertension in Japanese: how could Japan get longevity? EPMA J. 2011; 2(1):59-64. doi: 10.1007/s13167-011-0069-y pmid: 3405372
[17]	Dalai N, Cui H, Yan M, Rile G, Li S, Su X . Risk factors for the development of essential hypertension in a Mongolian population of China: a case-control study. Genet Mol Res, 2014,13(2):3283-3291 doi: 10.4238/2014.April.29.6
[18]	Ulasi II, Ijoma CK, Onwubere BJ, Arodiwe E, Onodugo O, Okafor C . High prevalence and low awareness of hypertension in a market population in Enugu, Nigeria. Int J Hypertens, 2011,2011:869675 doi: 10.4061/2011/869675 pmid: 3038598
[19]	Vaidya A, Pathak RP, Pandey MR . Prevalence of hypertension in Nepalese community triples in 25 years: a repeat cross-sectional study in rural Kathmandu. Indian Heart J, 2012,64(2):128-131 doi: 10.1016/S0019-4832(12)60045-5
[20]	Ganesh Kumar S, Deivanai Sundaram N . Prevalence and risk factors of hypertension among bank employees in urban Puducherry, India. Int J Occup Environ Med, 2014,5(2):94-100 doi: 10.3126/kumj.v12i4.13728 pmid: 24748000
[21]	Bhadoria AS, Kasar PK, Toppo NA, Bhadoria P, Pradhan S, Kabirpanthi V . Prevalence of hypertension and associated cardiovascular risk factors in Central India. J Family Community Med, 2014,21(1):29-38 doi: 10.4103/2230-8229.128775 pmid: 24695988
[22]	Kojori J, Rahimi R . Effect of “no added salt diet” on blood pressure control and 24 hour urinary sodium excretion in mild to moderate hypertension. BMC Cardiovasc Disord, 2007,7:34 doi: 10.1186/1471-2261-7-34
[23]	He FJ, Campbell NR, MacGregor GA . Reducing salt intake to prevent hypertension and cardiovascular disease. Rev Panam Salud Publica, 2012,32(4):293-300 doi: 10.1590/S1020-49892012001000008 pmid: 23299291
[24]	de Brito-Ashurst I, Perry L, Sanders TA, Thomas JE, Dobbie H, Varagunam M, Yaqoob MM . The role of salt intake and salt sensitivity in the management of hypertension in South Asian people with chronic kidney disease: a randomised controlled trial. Heart, 2013,99(17):1256-1260 doi: 10.1136/heartjnl-2013-303688
[25]	Zhao X, Yin X, Li X, Yan LL, Lam CT, Li S, He F, Xie W, Sang B, Luobu G, Ke L, Wu Y . Using a low-sodium, high-potassium salt substitute to reduce blood pressure among Tibetans with high blood pressure: A patient-blinded randomized controlled trial. PLoS One, 2014,9(10):e110131 doi: 10.1371/journal.pone.0110131
[26]	Kawano Y, Abe H, Kojima S, Takishita S, Matsuoka H . Effects of repeated alcohol intake on blood pressure and sodium balance in Japanese males with hypertension. Hypertens Res, 2004,27(3):167-172 doi: 10.1291/hypres.27.167
[27]	Svetkey LP, Erlinger TP, Vollmer WM, Feldstein A, Cooper LS, Appel LJ, Ard JD, Elmer PJ, Harsha D, Stevens VJ . Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age. J Hum Hypertens, 2005,19(1):21-31 doi: 10.1038/sj.jhh.1001770 pmid: 3222215385946
[28]	Fodor JG, Whitmore B, Leenen F, Larochelle P . Lifestyle modifications to prevent and control hypertension. 5. Recommendations on dietary salt. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada. CMAJ, 1999,160(9 Suppl):S29-S34
[29]	Elliott P, Walker LL, Little MP, Blair-West JR, Shade RE, Lee DR, Rouquet P, Leroy E, Jeunemaitre X, Ardaillou R, Paillard F, Meneton P, Denton DA . Change in salt intake affects blood pressure of Chimpanzees: implications for human by populations. Circulation, 2007,116(14):1563-1568 doi: 10.1161/CIRCULATIONAHA.106.675579
[30]	Dobrian AD, Davies MJ, Schriver SD, Lauterio TJ, Prewitt RL . Oxidative stress in a rat model of obesity-induced hypertension. Hypertension, 2001,37(2 Pt 2):554-560 doi: 10.1161/01.HYP.37.2.554 pmid: 11230334
[31]	Wang W, Cui Y, Shen J, Jiang J, Chen S, Peng J, Wu Q . Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks. Hypertension, 2012,60(5):1352-1358 doi: 10.1161/HYPERTENSIONAHA.112.201244
[32]	Afolabi AO, Mudashiru SK, Alagbonsi IA . Effects of salt-loading hypertension on nociception in rats. J Pain Res, 2013,6:387-392 doi: 10.2147/JPR.S44206
[33]	Dahl LK, Heine M, Tassinari L . Effects of chronic excess salt ingestion: Evidence that genetic factors play an important role in susceptibility to experimental hypertension. J Exp Med, 1962,115(6):1173-1190 doi: 10.1084/jem.115.6.1173
[34]	Ge Y, Bagnall A, Stricklett PK, Webb D, Kotelevtsev Y, Kohan DE . Combined knockout of collecting duct endothelin A and B receptors causes hypertension?and sodium retention. Am J Physiol Renal Physiol, 2008,295(6):F1635-F1640 doi: 10.1152/ajprenal.90279.2008
[35]	Oikawa R, Hosoda C, Nasa Y, Daicho T, Tanoue A, Tsujimoto G, Takagi N, Tanonaka K, Takeo S . Decreased susceptibility to salt-induced hypertension in subtotally nephrectomized mice lacking the vasopressin V1a receptor. Cardiovasc Res, 2010,87(1):187-194 doi: 10.1093/cvr/cvq034
[36]	Kawarazaki H, Ando K, Fujita M, Matsui H, Nagae A, Muraoka K, Kawarasaki C, Fujita T . Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats. Am J Physiol Renal Physiol, 2011,300(6):F1402-F1409 doi: 10.1152/ajprenal.00691.2010
[37]	Cohen HW, Hailpern SM, Fang J, Alderman MH . Sodium intake and mortality in the NHANES II follow-up study. Am J Med, 2006, 119(3): 275.e7-e14 doi: 10.1016/j.amjmed.2005.10.042 pmid: 16490476
[38]	Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, Jin Y, Olszanecka A, Malyutina S, Casiglia E, Filipovsky J, Kawecka-Jaszcz K, Nikitin Y, Staessen JA ; European Project on Genes in Hypertension (EPOGH) Investigators.Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA, 2011,305(17):1777-1785 doi: 10.1001/jama.2011.574
[39]	He FJ, Appel LJ, Cappuccio FP, de Wardener HE, MacGregor GA. Does reducing salt intake increase cardiovascular mortality? Kidney Int. 2011; 80:696-698. doi: 10.1038/ki.2011.246 pmid: 21814179
[40]	Linde CI, Karashima E, Raina H, Zulian A, Wier WG, Hamlyn JM, Ferrari P, Blaustein MP, Golovina VA . Increased arterial smooth muscle Ca2+ signaling, vasoconstriction, and myogenic reactivity in Milan hypertensive rats. Am J Physiol Heart Circ Physiol, 2012,302(3):H611-H620 doi: 10.1152/ajpheart.00950.2011
[41]	Padilha AS, Salaices M, Vassallo DV, Batista PR, Siman FD . Hypertensive effects of the iv administration of picomoles of ouabain. Braz J Med Biol Res, 2011,44(9):933-938 doi: 10.1590/S0100-879X2011007500103 pmid: 21956536
[42]	Pulina MV, Zulian A, Berra-Romani R, Beskina O, Mazzocco-Spezzia A, Baryshnikov SG, Papparella I, Hamlyn JM, Blaustein MP, Golovina VA . Upregulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain-induced hypertensive rats. Am J Physiol Heart Circ Physiol, 2010,298(1):H263-H274 doi: 10.1152/ajpheart.00784.2009
[43]	Takahashi H, Yoshika M, Komiyama Y, Nishimura M . The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain. Hypertens Res, 2011,34(11):1147-1160 doi: 10.1038/hr.2011.105
[44]	Wenceslau CF, Davel AP, Xavier FE, Rossoni LV . Long-term ouabain treatment impairs vascular function in resistance arteries. J Vasc Res, 2011,48(4):316-326 doi: 10.1159/000322576 pmid: 21273786
[45]	Hamlyn JM, Manunta P . Endogenous ouabain: a link between sodium intake and hypertension. Curr Hypertens Rep, 2011,13(1):14-20 doi: 10.1007/s11906-010-0161-z pmid: 20972650
[46]	Blaustein MP, Leenen FH, Chen L, Golovina VA, Hamlyn JM, Pallone TL, Van Huysse JW, Zhang J, Wier WG . How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension. Am J Physiol Heart Circ Physiol, 2012,302(5):H1031-H1049 doi: 10.1152/ajpheart.00899.2011
[47]	Liu M, Ren Y, Guo C . Effect of ouabain on the pathogenesis of hypertension in rats. Chin Med J (Engl), 2014,127(10):1931-1934 doi: 10.3760/cma.j.issn.0366-6999.20131594 pmid: 24824258
[48]	Zulian A, Linde CI, Pulina MV, Baryshnikov SG, Papparella I, Hamlyn JM, Golovina VA . Activation of c-SRC underlies the differential effects of ouabain and digoxin on Ca2+ signaling in arterial smooth muscle cells. Am J Physiol Cell Physiol, 2013,304(4):C324-C333 doi: 10.1152/ajpcell.00337.2012
[49]	Blaustein MP . Endogenous ouabain: role in the pathogenesis of hypertension. Kidney Int, 1996,49(6):1748-1753 doi: 10.1038/ki.1996.260 pmid: 8743490
[50]	Boegehold MA . The effect of high salt intake on endothelial function: reduced vascular nitric oxide in the absence of hypertension. J Vasc Res, 2013,50(6):458-467 doi: 10.1159/000355270
[51]	Lob HE, Vinh A, Li L, Blinder Y, Offermanns S, Harrison DG . Role of vascular extracellular superoxide dismutase in hypertension. Hypertension, 2011,58(2):232-239 doi: 10.1161/HYPERTENSIONAHA.111.172718 pmid: 3376381
[52]	Kusche-Vihrog K, Jeggle P, Oberleithner H . The role of ENaC in vascular endothelium. Pflugers Arch, 2014,466(5):851-859 doi: 10.1007/s00424-013-1356-3 pmid: 24046153
[53]	Korte S, Str?ter AS, Drüppel V, Oberleithner H, Jeggle P, Grossmann C, Fobker M, Nofer JR, Brand E, Kusche-Vihrog K . Feedforward activation of endothelial ENaC by high sodium. FASEB J. 2014; pii: fj.14-250282. doi: 10.1096/fj.14-250282 pmid: 24868010

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