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Excess Body Weight, Insulin Resistance and Isolated Systolic Hypertension: Potential Pathophysiological Links

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Abstract

Isolated systolic hypertension, the most common form of hypertension in the elderly, but also detectable among young and middle-aged subjects, is independently associated with higher risk of cardiovascular events and all-cause mortality. Among various pathophysiological changes associated with aging, excess body weight and insulin resistance may predispose to this type of hypertension. Overweight or frank obesity and their frequent companion insulin resistance could mediate the development of isolated systolic hypertension through increase in the renin–angiotensin–aldosterone system activity, in the sympathetic tone and in salt-sensitivity, all in turn leading to endothelial dysfunction, arterial stiffness and increase in blood pressure. This review will focus on this cluster of pathophysiological factors and on the mechanistic pathways whereby they may favor the development of isolated systolic hypertension.

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References

  1. Yano Y, Lloyd-Jones DM. Isolated systolic hypertension in young and middle-aged adults. Curr Hypertens Rep. 2016;18:78.

    Article  PubMed  Google Scholar 

  2. Conen D, Bamberg F. Noninvasive 24-h ambulatory blood pressure and cardiovascular disease: a systematic review and meta-analysis. J Hypertens. 2008;26(7):1290–9.

    Article  CAS  PubMed  Google Scholar 

  3. Ekundayo OJ, Allman RM, Sanders PW, Aban I, Love TE, Arnett D, Ahmed A. Isolated systolic hypertension and incident heart failure in older adults: a propensity matched study. Hypertension. 2009;53(3):458–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li Y, Wei FF, Thijs L, Boggia J, Asayama K, Hansen TW, Kikuya M, Björklund-Bodegård K, Ohkubo T, Jeppesen J, Gu YM, Torp-Pedersen C, Dolan E, Liu YP, Kuznetsova T, Stolarz-Skrzypek K, Tikhonoff V, Malyutina S, Casiglia E, Nikitin Y, Lind L, Sandoya E, Kawecka-Jaszcz K, Mena L, Maestre GE, Filipovský J, Imai Y, O’Brien E, Wang JG, Staessen JA, International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO) Investigators. Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations. Circulation. 2014;130(6):466–74.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957–67.

    Article  PubMed  Google Scholar 

  6. Yano Y, Stamler J, Garside DB, Daviglus ML, Franklin SS, Carnethon MR, Liu K, Greenland P, Lloyd-Jones DM. Isolated systolic hypertension in young and middle-aged adults and 31-year risk for cardiovascular mortality: the Chicago Heart Association Detection Project in Industry study. J Am Coll Cardiol. 2015;65:327–35.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Franklin SS, Gustin W, Wong ND, Larson MG, Weber MA, Kannel WB, Levy D. Hemodynamic patterns of age-related changes in blood pressure The Framingham Heart Study. Circulation. 1997;96(1):308–15.

    Article  CAS  PubMed  Google Scholar 

  8. Chobanian AV. Clinical practice. Isolated systolic hypertension in the elderly. N Engl J Med. 2007;357(8):789–96.

    Article  CAS  PubMed  Google Scholar 

  9. Franklin SS. Elderly hypertensives: how are they different? J Clin Hypertens (Greenwich). 2012;14(11):779–86.

    Article  Google Scholar 

  10. World Health Organization. Obesity: preventing and managing the global epidemic [WHO technical report series #894]. Geneva: World Health Organization; 2000.

    Google Scholar 

  11. Adams KF, Schatzkin A, Harris TB, Kipnis V, Mouw T, Ballard-Barbash R, Hollenbeck A, Leitzmann MF. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med. 2006;355:763–78.

    Article  CAS  PubMed  Google Scholar 

  12. Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke. 2010;41(5):e418–26.

    Article  PubMed  Google Scholar 

  13. Aronne LJ, Brown WV, Isoldi KK. Cardiovascular disease in obesity: a review of related risk factors and risk reduction strategies. J Clin Lipidol. 2007;1:575–82.

    Article  PubMed  Google Scholar 

  14. Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab. 2009;94:3171–82.

    Article  CAS  PubMed  Google Scholar 

  15. Herder C, Haastert B, Muller-Scholze S, et al. Association of systemic chemokine concentrations with impaired glucose tolerance and type 2 diabetes: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4). Diabetes. 2005;54:S11–7.

    Article  CAS  PubMed  Google Scholar 

  16. Rimm EB, Stampfer MJ, Giovannucci E, Ascherio A, Spiegelman D, Colditz GA, Willett WC. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am J Epidemiol. 1995;141:1117–27.

    Article  CAS  PubMed  Google Scholar 

  17. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68:975–81.

    Article  CAS  PubMed  Google Scholar 

  18. Olefsky JM. The insulin receptor: its role in insulin resistance of obesity and diabetes. Diabetes. 1976;25:1154–62.

    Article  CAS  PubMed  Google Scholar 

  19. Caro JF, Sinha MK, Raju SM, Ittoop O, Pories WJ, Flickinger EG, Meelheim D, Dohm GL. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. J Clin Investig. 1987;79:1330–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation, and atherogenesis. Endocrinology. 2003;144:2195–200.

    Article  CAS  PubMed  Google Scholar 

  21. Tousoulis D, Antoniades C, Stefanadis C. Assessing inflammatory status in cardiovascular disease. Heart. 2007;93:1001–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bender SB, McGraw AP, Jaffe IZ, Sowers JR. Mineralocorticoid receptor-mediated vascular insulin resistance: an early contributor to diabetes-related vascular disease? Diabetes. 2013;62:313–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Investig. 2006;116:1494–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Amasyali B, Kose S, Kursaklioglu H, Kilic A, Isik E. Leptin in acute coronary syndromes: has the time come for its use in risk stratification? Int J Cardiol. 2008;130(2):264–5.

    Article  PubMed  Google Scholar 

  25. Carlyle M, Jones OB, Kuo JJ, Hall JE. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension. 2002;39:496–501.

    Article  CAS  PubMed  Google Scholar 

  26. Galletti F, D’Elia L, Barba G, Siani A, Cappuccio FP, Farinaro E, Iacone R, Russo O, De Palma D, Ippolito R, Strazzullo P. High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study. J Clin Endocrinol Metab. 2008;93(10):3922–6.

    Article  CAS  PubMed  Google Scholar 

  27. Frayn KN. Obesity and metabolic disease: is adipose tissue the culprit? Proc Nutr Soc. 2005;64:7–13.

    Article  PubMed  Google Scholar 

  28. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.

    Article  CAS  PubMed  Google Scholar 

  29. Doronzo G, Russo I, Mattiello L, Anfossi G, Bosia A, Trovati M. Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance. Eur J Clin Investig. 2004;34:664–73.

    Article  CAS  Google Scholar 

  30. Torjesen AA, Sigurðsson S, Westenberg JJ, Gotal JD, Bell V, Aspelund T, Launer LJ, de Roos A, Gudnason V, Harris TB, Mitchell GF. Pulse pressure relation to aortic and left ventricular structure in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Hypertension. 2014;64:756–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. DeMarco VG, Habibi J, Jia G, Aroor AR, Ramirez-Perez FI, Martinez-Lemus LA, Bender SB, Garro M, Hayden MR, Sun Z, Meininger GA, Manrique C, Whaley-Connell A, Sowers JR. Low-dose mineralocorticoid receptor blockade prevents western diet-induced arterial stiffening in female mice. Hypertension. 2015;66:99–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chung AW, Yang HH, Sigrist MK, Brin G, Chum E, Gourlay WA, Levin A. Matrix metalloproteinase-2 and -9 exacerbate arterial stiffening and angiogenes is in diabetes and chronic kidney disease. Cardiovasc Res. 2009;84:494–504.

    Article  CAS  PubMed  Google Scholar 

  33. Poirier P, Martin J, Marceau P, Biron S, Marceau S. Impact of bariatric surgery on cardiac structure, function and clinical manifestations in morbid obesity. Expert Rev Cardiovasc Ther. 2004;2:193–201.

    Article  PubMed  Google Scholar 

  34. Seifalian AM, Filippatos TD, Joshi J, Mikhailidis DP. Obesity and arterial compliance alterations. Curr Vasc Pharmacol. 2010;8(2):155–68.

    Article  CAS  PubMed  Google Scholar 

  35. Selcuk A, Bulucu F, Kalafat F, Cakar M, Demirbas S, Karaman M, Ay SA, Saglam K, Balta S, Demirkol S, Arslan E. Skinfold thickness as a predictor of arterial stiffness: obesity and fatness linked to higher stiffness measurements in hypertensive patients. Clin Exp Hypertens. 2013;35(6):459–64.

    Article  PubMed  Google Scholar 

  36. Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: PartI. Circulation. 2003;108:1527–32.

    Article  PubMed  Google Scholar 

  37. Gorzelniak K, Engeli S, Janke J, Luft FC, Sharma AM. Hormonal regulation of the human adipose-tissue renin–angiotensin system: relationship to obesity and hypertension. J Hypertens. 2002;20(5):965–73.

    Article  CAS  PubMed  Google Scholar 

  38. Cote AT, Harris KC, Panagiotopoulos C, Sandor GG, Devlin AM. Childhood obesity and cardiovascular dysfunction. J Am Coll Cardiol. 2013;62:1309–19.

    Article  PubMed  Google Scholar 

  39. Zucker IH. Novelmecha- nisms of sympathetic regulation in chronic heart failure. Hypertension. 2006;48:1005–11.

    Article  CAS  PubMed  Google Scholar 

  40. Taddei S, Virdis A, Mattei P, Favilla S, Salvetti A. Angiotensin II and sympathetic activity in sodium-restricted essential hypertension. Hypertension. 1995;25:595–601.

    Article  CAS  PubMed  Google Scholar 

  41. Reid IA. Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol. 1992;262:E763–78.

    CAS  PubMed  Google Scholar 

  42. Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M, ThÖne-Reineke C, Unger T, Kintscher U. PPARgamma- activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension. 2005;46(1):137–43.

    Article  CAS  PubMed  Google Scholar 

  43. Mahmud A, Feely J. Arterial stiffness and the renin–angiotensin–aldosterone system. J Renin Angiotensin Aldosterone Syst. 2004;5(3):102–8.

    Article  CAS  PubMed  Google Scholar 

  44. Rompe F, Artuc M, Hallberg A, Alterman M, Ströder K, Thöne-Reineke C, Reichenbach A, Schacherl J, Dahlöf B, Bader M, Alenina N, Schwaninger M, Zuberbier T, Funke-Kaiser H, Schmidt C, Schunck WH, Unger T, Steckelings UM. Direct angiotensin II type 2 receptor stimulation acts anti-inflammatory through epoxyeicosatrienoic acid and inhibition of nuclear factor kappaB. Hypertension. 2010;55(4):924–31.

    Article  CAS  PubMed  Google Scholar 

  45. Wallin BG, Charkoudian N. Sympathetic neural control of integrated cardiovascular function: insights from measurement of human sympathetic nerve activity. Muscle Nerve. 2007;36:595–614.

    Article  CAS  PubMed  Google Scholar 

  46. Katovich MJ, Pachori A. Effects of inhibition of the renin–angiotensin system on the cardiovascular actions of insulin. Diabetes Obes Metab. 2000;2(1):3–14.

    Article  CAS  PubMed  Google Scholar 

  47. Grassi G, Dell’Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia G. Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens. 2004;22:2363–9.

    Article  CAS  PubMed  Google Scholar 

  48. Patel KP, Li YF, Hirooka Y. Role of nitric oxide in central sympathetic outflow. Exp Biol Med (Maywood). 2001;226:814–24.

    Article  CAS  PubMed  Google Scholar 

  49. Bruijns RH, VanKleef EM, Smits JF, DeMey JG, Daemen MJ. Effects of chemical sympathectomy on angiotensin II-induced neo intimal growth in the balloon-injured rat carotid artery. J Vasc Res. 1998;35:124–33.

    Article  CAS  PubMed  Google Scholar 

  50. Swierblewska E, Hering D, Kara T, Kunicka K, Kruszewski P, Bieniaszewski L, Boutouyrie P, Somers VK, Narkiewicz K. An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens. 2010;28(5):979–84.

    Article  CAS  PubMed  Google Scholar 

  51. Boutouyrie P, Lacolley P, Girerd X, Beck L, Safar M, Laurent S. Sympathetic activation decreases radial artery compliance in humans. Am J Physiol. 1994;267:H1368–76.

    CAS  PubMed  Google Scholar 

  52. Mangoni AA, Mircoli L, Giannattasio C, Mancia G, Ferrari AU. Effects of sympathectomy on mechanical properties of common carotid and femoral arteries. Hypertension. 1997;30:1085–8.

    Article  CAS  PubMed  Google Scholar 

  53. Failla M, Grappiolo A, Emanuelli G, Vitale G, Fraschini N, Giannattasio C, Mancia G. Sympathetic tone restrains arterial distensibility of healthy and atherosclerotic subjects. J Hypertens. 1999;17:1117–24.

    Article  CAS  PubMed  Google Scholar 

  54. World Health Organization. Reducing salt intake in populations: report of a WHO forum and technical meeting. Geneva: WHO; 2007. p. 1–60.

    Google Scholar 

  55. Donfrancesco C, Ippolito R, Lo Noce C, Palmieri L, Iacone R, Russo O, Vanuzzo D, Galletti F, Galeone D, Giampaoli S, Strazzullo P. Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study. Nutr Metab Cardiovasc Dis. 2013;23:850–6.

    Article  CAS  PubMed  Google Scholar 

  56. He FJ, Markandu ND, MacGregor GA. Modest salt reduction lowers blood pressure in isolated systolic hypertension and combined hypertension. Hypertension. 2005;46(1):66–70.

    Article  CAS  PubMed  Google Scholar 

  57. Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell’Italia LJ, Calhoun DA. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54:475–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  59. Strazzullo P, Galletti F, Dessì-Fulgheri P, Ferri C, Glorioso N, Malatino L, Mantero F, Manunta P, Semplicini A, Ghiadoni L, Zoccali C. Prediction and consistency of blood pressure salt-sensitivity as assessed by a rapid volume expansion and contraction protocol. Salt-Sensitivity Study Group of the Italian Society of Hypertension. J Nephrol. 2000;13:46–53.

    CAS  PubMed  Google Scholar 

  60. Strazzullo P, Galletti F, Barba G. Altered renal handling of sodium in human hypertension: short review of the evidence. Hypertension. 2003;41:1000–5.

    Article  CAS  PubMed  Google Scholar 

  61. Galletti F, Strazzullo P, Ferrara I, Annuzzi G, Rivellese AA, Gatto S, Mancini M. NaCl sensitivity of essential hypertensive patients is related to insulin resistance. J Hypertens. 1997;15:1485–91.

    Article  CAS  PubMed  Google Scholar 

  62. Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, Martin M. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med. 1989;321:580–5.

    Article  CAS  PubMed  Google Scholar 

  63. Strazzullo P, Barbato A, Galletti F, Barba G, Siani A, Iacone R, D’Elia L, Russo O, Versiero M, Farinaro E, Cappuccio FP. Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study. J Hypertens. 2006;24:1633–9.

    Article  CAS  PubMed  Google Scholar 

  64. Chen J, Gu D, Huang J, Rao DC, Jaquish CE, Hixson JE, Chen CS, Chen J, Lu F, Hu D, Rice T, Kelly TN, Hamm LL, Whelton PK, He J, GenSalt Collaborative Research Group. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373:829–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Strazzullo P, Barba G, Cappuccio FP, Siani A, Trevisan M, Farinaro E, Pagano E, Barbato A, Iacone R, Galletti F. Altered renal sodium handling in men with abdominal adiposity: a link to hypertension. J Hypertens. 2001;19:2157–64.

    Article  CAS  PubMed  Google Scholar 

  66. Barbato A, Cappuccio FP, Folkerd EJ, Strazzullo P, Sampson B, Cook DG, Alberti KG. Metabolic syndrome and renal sodium handling in three ethnic groups living in England. Diabetologia. 2004;47:40–6.

    Article  CAS  PubMed  Google Scholar 

  67. Barba G, Russo O, Siani A, Iacone R, Farinaro E, Gerardi MC, Russo P, Della Valle E, Strazzullo P. Plasma leptin and blood pressure in men: graded association independent of body mass and fat pattern. Obes Res. 2003;11:160–6.

    Article  PubMed  Google Scholar 

  68. Bragulat E, de la Sierra A, Antonio MT, Coca A. Endothelial dysfunction in salt-sensitive essential hypertension. Hypertension. 2001;37:444–8.

    Article  CAS  PubMed  Google Scholar 

  69. Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O’Rourke MF. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation. 1985;71:202–10.

    Article  CAS  PubMed  Google Scholar 

  70. Avolio AP, Clyde KM, Beard TC, Cooke HM, Ho KK, O’Rourke MF. Improved arterial distensibility in normotensive subjects on a low salt diet. Arteriosclerosis. 1986;6:166–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  72. Frohlich ED. The salt conundrum: a hypothesis. Hypertension. 2007;50:161–6.

    Article  CAS  PubMed  Google Scholar 

  73. Ying W-Z, Sanders PW. Dietary salt increases endothelial nitric oxide synthase and TGF-β1 in rat aortic endothelium. Am J Physiol. 1999;277(4 Pt 2):H1293–8.

    CAS  PubMed  Google Scholar 

  74. Ying W-Z, Sanders PW. Dietary salt modulates renal production of transforming growth factor-β in rats. Am J Physiol. 1998;274(4 Pt 2):F635–41.

    CAS  PubMed  Google Scholar 

  75. Matavelli LC, Zhou X, Varagic J, Susic D, Frohlich ED. Salt loading produces severe renal hemodynamic dysfunction independent of arterial pressure in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2007;292:H814–9.

    Article  CAS  PubMed  Google Scholar 

  76. Kocks MJ, Buikema H, Gschwend S, Boomsma F, de Zeeuw D, Navis G. High dietary sodium blunts affects of angiotensin-converting enzyme inhibition on vascular angiotensin I-to-angiotensin II conversion in rats. J Cardiovasc Pharmacol. 2003;42:601–6.

    Article  CAS  PubMed  Google Scholar 

  77. Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, Yasukawa H, Iwami G, Okuda S, Imaizumi T. Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension. 1997;29(1 Pt 2):242–7.

    Article  CAS  PubMed  Google Scholar 

  78. 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 

  79. Oberleithner H, Peters W, Kusche-Vihrog K, Korte S, Schillers H, Kliche K, Oberleithner K. Salt overload damages the glycocalyx sodium barrier of vascular endothelium. Pflugers Arch. 2011;462(4):519–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Leenen FH, Ruzicka M, Huang BS. The brain and salt-sensitive hypertension. Curr Hypertens Rep. 2002;4:129–35.

    Article  PubMed  Google Scholar 

  81. King AJ, Novotny M, Swain GM, Fink GD. Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1262–7.

    Article  CAS  PubMed  Google Scholar 

  82. Jacob F, Clark LA, Guzman PA, Osborn JW. Role of renal nerves in development of hypertension in DOCA-salt model in rats: a telemetric approach. Am J Physiol Heart Circ Physiol. 2005;289:H1519–29.

    Article  CAS  PubMed  Google Scholar 

  83. King AJ, Osborn JW, Fink GD. Splanchnic circulation is a critical neural target in angiotensin II salt hypertension in rats. Hypertension. 2007;50:547–56.

    Article  CAS  PubMed  Google Scholar 

  84. Stocker SD, Madden CJ, Sved AF. Excess dietary salt intake alters the excitability of central sympathetic networks. Physiol Behav. 2010;100(5):519–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ciura S, Bourque CW. Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. J Neurosci. 2006;26(35):9069–75.

    Article  CAS  PubMed  Google Scholar 

  86. Brooks VL, Freeman KL, O’Donaughy TL. Acute and chronic increases in osmolality increase excitatory amino acid drive of the rostral ventrolateral medulla in rats. Am J Physiol Regul Integr Comp Physiol. 2004;287(6):R1359–68.

    Article  CAS  PubMed  Google Scholar 

  87. Weiss ML, Claassen DE, Hirai T, Kenney MJ. Nonuniform sympathetic nerve responses to intravenous hypertonic saline infusion. J Auton Nerv Syst. 1996;57(1–2):109–15.

    Article  CAS  PubMed  Google Scholar 

  88. Farquhar WB, Paul EE, Prettyman AV, Stillabower ME. Blood pressure and hemodynamic responses to an acute sodium load in humans. J Appl Physiol. 2005;99(4):1545–51.

    Article  PubMed  Google Scholar 

  89. Farquhar WB, Wenner MM, Delaney EP, Prettyman AV, Stillabower ME. Sympathetic neural responses to increased osmolality in humans. Am J Physiol Heart Circ Physiol. 2006;291(5):H2181–6.

    Article  CAS  PubMed  Google Scholar 

  90. Peskind ER, Radant A, Dobie DJ, Hughes J, Wilkinson CW, Sikkema C, Veith RC, Dorsa DM, Raskind MA. Hypertonic saline infusion increases plasma norepinephrine concentrations in normal men. Psychoneuroendocrinology. 1993;18(2):103–13.

    Article  CAS  PubMed  Google Scholar 

  91. Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009;24(339):b4567.

    Article  Google Scholar 

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Correspondence to Pasquale Strazzullo.

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PS is scientific coordinator of the Interdisciplinary Working Group for Reduction of Salt Intake in Italy (GIRCSI) and an unpaid member of WASH (World Action in Salt and Health). LD has no conflicts of interest to declare.

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D’Elia, L., Strazzullo, P. Excess Body Weight, Insulin Resistance and Isolated Systolic Hypertension: Potential Pathophysiological Links. High Blood Press Cardiovasc Prev 25, 17–23 (2018). https://doi.org/10.1007/s40292-017-0240-1

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