Skip to main content
SpringerLink
Log in

Alterations in sodium metabolism as an etiological model for hypertension

  • Review
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Summary

An adequate matching for race, sex, stage of the menstrual cycle, family history of hypertension, and the amount of sodium and other electrolytes in the diet should be a prerequisite for valid conclusions when interpreting the erythrocyte concentration and fluxes of sodium in essential hypertensive patients in comparison with normal subjects. Alterations in intracellular sodium concentration and transmembrane sodium transport systems as causes of essential hypertension are postulated. This review article describes how this abnormal sodium and calcium metabolism translates into increased systemic vascular resistance through altered vasoactive responses and/or vasculature structural changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lee C, Dagostino M. Effect of strophantidin on the intracellular Na+ activity and twitch tension of constantly driven canine cardiac Purkinje fibers.Biophys J 1982;40:185–198.

    Google Scholar 

  2. Akera T, Brody T. Estimating sodium pump activity in beating heart muscle.Trends Pharmacol Sci 1985;6:156–159.

    Google Scholar 

  3. Whittaker J, Hawkins M., Swaminathan R. Changes in erythrocyte sodium, sodium transport and3H-ouabain binding capacity during digoxin administration in the pig.Life Sci 1983;32:747–754.

    Google Scholar 

  4. Post RL, Merritt CR, Kinsolving CR, et al. Membrane adenosine triphosphatase as a participant in the active transport of sodium and potassium in human erythrocytes.J Biol Chem 1960;235:1796–1802.

    Google Scholar 

  5. Beutler E, Kuhl W. Guanosine triphosphatase activity in human erythrocyte membrane.Biochem Biophys Acta 1980;601:372–379.

    Google Scholar 

  6. De Luise M, Blackburn GM, Flier JS. Reduced activity of the red cell sodium-potassium pump in human obesity.N Engl J Med 1980;305:1017–1022.

    Google Scholar 

  7. Bernstein JC, Israel Y. Active transport of Rb86 in human red cells and rat brain slices.J Pharmacol Exp Ther 1970;174:323–329.

    Google Scholar 

  8. Love WD, Burch GE. A comparison of potassium42, rubidium86, cesium134 as tracers of potassium in the study of cation metabolism of human erythrocytes in vitro.J Lab Clin Med 1953;41:351–357.

    Google Scholar 

  9. Sachs JR, Welt LG. The concentration dependence of active potassium transport in the human red blood cell.J Clin Invest 1967;46:65–76.

    Google Scholar 

  10. Cumberbatch M, Morgan DB. Relations between sodium transport and sodium concentration in human erythrocytes in health and disease.Clin Sci 1981;60:555–564.

    Google Scholar 

  11. Hoffman JF, Kregonov FM. The characterization of new energy-dependent cation transport process in red blood cells.Ann NY Acad Sci 1966;137:566–586.

    Google Scholar 

  12. Chipperfield AR. Chloride dependence of frusemide- and phloretin-sensitive sodium and potassium fluxes in human red cells.J Physiol 1981;312:435–444.

    Google Scholar 

  13. Dunham PB, Stewart GW, Ellory JC. Chloride-activated potassium transport in human erythrocytes.Proc Natl Acad Sci USA 1980;77:7711–7715.

    Google Scholar 

  14. Wiley JC, Cooper RA. A furosemide-sensitive cotransport of sodium plus potassium in the human red cell.J Clin Invest 1974;53:745–755.

    Google Scholar 

  15. Brand SC, Whittam R. The effect of furosemide on sodium movements in human red blood cells.J Physiol 1984;348:301–306.

    Google Scholar 

  16. Frizzell RA, Field M, Schultz SG. Sodium-coupled chloride transport by epithelial tissues.Am J Physiol 1979;236:F1-F8.

    Google Scholar 

  17. Burg HB. Thick ascending limb of Henle's loop.Kidney Int 1982;22:454–464.

    Google Scholar 

  18. Sachs JR. Ouabain-insensitive sodium movements in the human red blood cell.J Gen Physiol 1971;57:259–282.

    Google Scholar 

  19. Garay RP, Meyer P. A new test showing abnormal net Na+ and K+ fluxes in erythrocytes of essential hypertensive patients.Lancet 1979;1:349–353.

    Google Scholar 

  20. Duhm J, Göbel BO. Sodium-lithium exchange and sodiumpotassium countertransport in human erythrocytes. 1. Evaluation of a simple uptake test to assess the activity of two transport systems.Hypertension 1982;4:468–476.

    Google Scholar 

  21. Ussing HH. Transport of ions across cellular membranes.Physiol Rev 1949;29:127–133.

    Google Scholar 

  22. Duhm J, Eisenried F, Becker BF, et al. Studies of the lithium transport across the red cell membrane. 1. Li-uphill transport by the Na-dependent Li-countertransport system in human erythrocytes.Pflügers Arch 1976;364:147–155.

    Google Scholar 

  23. Haas M, Schooler J, Tosteson C. Coupling of lithium to sodium transport in human red cells.Nature 1975;258:425–427.

    Google Scholar 

  24. Pandey GN, Sarkadi B, Haas M, et al. Lithium transport pathways in human red blood cells.J Gen Physiol 1978;72:233–248.

    Google Scholar 

  25. Morgan K, Brown RC, Spurlock G, et al. Inhibitin: A specific inhibitor of sodium/sodium exchange in erythrocyte.J Clin Invest 1986;77:538–544.

    Google Scholar 

  26. Dissing S, Hoffman JF. Ouabain-insensitive Na-efflux from human red blood cells stimulated by outside H, Na or Li ions.J Gen Physiol 1982;80:15a.

    Google Scholar 

  27. Canessa M, Adragna N, Solomon H, et al. Increased sodium-lithium countertransport in red cells of patients with essential hypertension.N Engl J Med 1980;302:772–776.

    Google Scholar 

  28. Kleyman TR, Cragoe EJ Jr. Amiloride and its analogs as tools in the study of ion transport.J Membr Biol 1988;105:1–21.

    Google Scholar 

  29. Dennis SC, Coetzee WA, Cragoe EJ Jr, Opie LH. Effects of proton buffering and of amiloride derivatives on reperfusion arrhythmias in isolated rat hearts. Possible evidence for an arrhythmogenic role of Na+/H+ exchange.Circ Res 1990;66:1156–1159.

    Google Scholar 

  30. Scholz W, Albus U, Linz W, et al. Effects of Na+/H+ exchange inhibitors in cardiac ischemia.J Mol Cell Cardiol 1992;24:731–740.

    Google Scholar 

  31. Meng HP, Pierce GN. Protective effects of 5-(N-N-dimethyl) amiloride on ischemia-reperfusion injury in hearts.Am J Physiol 1990;258:H1615-H1619.

    Google Scholar 

  32. Scholz W, Albus U, Lang HJ, et al. Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischaemia.Br J Pharmacol 1993;109:562–568.

    Google Scholar 

  33. Sack S, Mohri M, Schwarz ER, et al. Effects of a new Na+/H+ antiporter inhibition on postischemic reperfusion in pig heart.J Cardiovasc Pharmacol 1994;23:72–78.

    Google Scholar 

  34. Garay RP, Hannaert PA, Nazaret C, Cragoe EJ Jr. The significance of the relative effects of loop diuretics and antibrain edema agents on the Na+,K+,Cl−-cotransport system and the Cl−/NaCO −3 anion exchange.Naunyn-Schmiedeberg Arch Pharmacol 1986;334:202–209.

    Google Scholar 

  35. Nazaret C, Diez J, Hannaert PA, et al. Inhibition of the Cl−/NaCO −3 anion exchanger by xipamide in human red blood cells.Eur J Pharmacol 1987;144:353–362.

    Google Scholar 

  36. Lijnen P, Fagard R, Staessen J, Amery A. In vitro effect of xipamide on sodium-potassium transport systems in human erythrocytes.Methods Find Exp Clin Pharmacol 1988;10:527–530.

    Google Scholar 

  37. Lijnen P, Amery A. Erythrocyte Na+ and K+ transport systems during long-term administration of the diuretic xipamide in men.Methods Find Exp Clin Pharmacol 1989;11:587–594.

    Google Scholar 

  38. Funder J, Tosteson DC, Wieth O. Effects of bicarbonate on lithium transport in human red cells.J Gen Physiol 1978;72:233–247.

    Google Scholar 

  39. Aderounmu AF, Salako LA. Abnormal cation composition and transport in erythrocytes from hypertensive patients.Eur J Clin Invest 1979;9:369–375.

    Google Scholar 

  40. Etkin NL, Mahoney JR, Forsthoefel MW, et al. Racial differences in hypertension-associated red cell sodium permeability.Nature 1982;297:588–589.

    Google Scholar 

  41. Fitzgibbon WR, Morgan TO, Meyers JB. Erythrocyte22Na efflux and urinary sodium excretion in essential hypertension.Clin Sci 1980;59(Suppl):195s-197s.

    Google Scholar 

  42. Henningsen NC, Mattson S, Nosslin B, et al. Abnormal whole body and cellular (erythrocytes) turnover of22Na in normotensive relatives of probands with established essential hypertension.Clin Sci 1979;57:321s-324s.

    Google Scholar 

  43. Mahoney JR, Etkin NL, McSwigan JD, et al. Assessment of red cell sodium transport in essential hypertension.Blood 1982;59:439–442.

    Google Scholar 

  44. Postnov YV, Orlov SN, Shevchenko AS, et al. Altered sodium permeability, calcium binding and Na-K-ATPase activity in red blood cell membrane in essential hypertension.Pflügers Arch 1977;371:263–269.

    Google Scholar 

  45. Wessels F, Junge-Hulsing G, Losse H. Untersuchungen zur Natriumpermeabilität der Erythrozyten bei Hypertonikern und Normotonikern mit familiärer Hochdruckbelastung.Z Kreislaufforsch 1967;56:374–380.

    Google Scholar 

  46. M'Buyamba-Kabangu JR, Lijnen P, Fagard R, Amery A. Intraerythrocyte sodium concentration in black families with and without hypertension.Methods Find Exp Clin Pharmacol 1986;8:437–442.

    Google Scholar 

  47. Losse H, Wehmeyer H, Wessels F. Der Wasser- und Elektrolytgehalt von Erythrozyten bei arterieller Hypertonie.Klin Wochenschr 1960;38:393–402.

    Google Scholar 

  48. Cole CH. Erythrocyte membrane sodium transport in patients with treated and untreated essential hypertension.Circulation 1983;68:17–22.

    Google Scholar 

  49. Gessler U. Intra- und extrazelluläre Elektrolytveränderungen bei essentieller Hypertonie vor und nach Behandlung.Zeitschr Kreislaufforsch 1961;51:177–183.

    Google Scholar 

  50. Milar JA, Bramley PM, Paulin JM, et al. Evidence against a circulating ouabain-like transport inhibitor as a cause of increased red cell sodium in essential hypertension.J Hypertens 1984;2(Suppl):461–463.

    Google Scholar 

  51. Montanari A, Borghi L, Canali M, et al. Altered sodium efflux in red blood cells from essential hypertensive subjects. In: Losse H, Zumkley H, eds.Intracellular Electrolytes and Arterial Hypertension. Stuttgart: Georg Thieme Verlag, 1980:135–144.

    Google Scholar 

  52. Saito K, Furuta Y, Sano H, et al. Abnormal relationship between dietary sodium intake and red cell sodium transport in salt-sensitive patients with essential hypertension.Clin Exp Hypertens 1985;A7:1217–1232.

    Google Scholar 

  53. Urry DW, Trapane TL, Andrews KS, et al. NMR observation of altered sodium interaction with human erythrocyte membranes of essential hypertensives.Biochem Biophys Res Commun 1980;96:514–521.

    Google Scholar 

  54. Ambrosioni E, Costa FV, Montebugnoli L, et al. Increased intralymphocytic sodium content in essential hypertension.Clin Sci 1981;61:181–186.

    Google Scholar 

  55. Araoye MA, Khatri IM, Yao LL, et al. Leukocyte intracellular cations in hypertension: Effect of antihypertensive drugs.Am Heart J 1978;96:731–738.

    Google Scholar 

  56. Boon NA, Harper C, Aronson JK, et al. Cation transport functions in vitro in patients with untreated essential hypertension: A comparison of erythrocytes and leucocytes.Clin Sci 1985;68:511–515.

    Google Scholar 

  57. Chien Y, Zhao G. Abnormal leucocyte sodium transport in Chinese patients with essential hypertension and their normotensive offspring.Clin Exp Hypertens 1984;A6:2279–2296.

    Google Scholar 

  58. Edmondson RPS, Thomas RD, Hilton PJ, et al. Abnormal cation composition and sodium transport in essential hypertension.Lancet 1975;1:1003–1005.

    Google Scholar 

  59. Poston L, Sewell RB, Williams R, et al. The effect of low molecular weight natriuretic substance and serum from hypertensive patients on the sodium transport of leucocytes from normal subjects. In: Zumkley H, Losse H, eds.Intracellular Electrolytes and Arterial Hypertension. Stuttgart: Georg Thieme Verlag, 1980:93–97.

    Google Scholar 

  60. Duhm J, Göbel B, Lorenz B, et al. Sodium-lithium exchange and sodium-potassium cotransport in human erythrocytes. Part 2: A simple uptake test applied to normotensive and essential hypertensive individuals.Hypertension 1982;4:477–482.

    Google Scholar 

  61. Walter U, Distler A. Abnormal sodium efflux in erythrocytes of patients with essential hypertension.Hypertension 1982;4:205–210.

    Google Scholar 

  62. Wiley JS, Clarke DA, Bonacquisto LA, et al. Erythrocyte cation cotransport and countertransport in essential hypertension.Hypertension 1984;6:630–638.

    Google Scholar 

  63. Minta A, Tsien RY. Fluorescent indicators for cytosolic sodium.J Biol Chem 1989;264:19449–19457.

    Google Scholar 

  64. Hurootunian AT, Kao JPY, Eckert BK, Tsien RY. Fluorescence ratio imaging of cytosolic free Na+ in individual fibroblasts and lymphocytes.J Biol Chem 1990;265:19458–19467.

    Google Scholar 

  65. Borin M, Siffert W. Stimulation by thrombin increases the cytosolic free Na+ concentration in human platelets.J Biol Chem 1990;265:19543–19550.

    Google Scholar 

  66. Tepel M, Bauer S, Husseini S, Zidek W. Reduced cytosolic free Na+ concentration in intact platelets of essential hypertensives.J Hypertens 1992;10:991–996.

    Google Scholar 

  67. Tepel M, Theilmeier G, Bachmann J, et al. Increased cytosolic sodium and reduced Na, K-ATPase activity in transgenic rats.Hypertension 1994;23(Suppl I): 198–202.

    Google Scholar 

  68. Blaustein MP. Sodium transport and hypertension. Where are we going?Hypertension 1984;6:445–453.

    Google Scholar 

  69. Erdmann E, Werdan K, Hegelberger R, et al. Determination of the number of (Na+-K+)ATPase, their enzymatic activity and the active Na+/K+ transport in human erythrocytes on hypokalaemia and hypertension. In: Zumkley H, Losse H, eds.Intracellular Electrolytes and Arterial Hypertension. Stuttgart: Georg Thieme Verlag, 1980: 164–170.

    Google Scholar 

  70. Swarts HGP, Bonting SL, de Pont JJ, et al. Cation fluxes and Na+,K+ activated ATPase activity in erythrocytes of patients with essential hypertension.Hypertension 1981;3:641–649.

    Google Scholar 

  71. Tuck ML, Gross C, Maxwell MM, et al. Erythrocyte Na+,K+-cotransport and Na+,K+ pump in blacks and Caucasian hypertensive patients.Hypertension 1984;6:536–544.

    Google Scholar 

  72. Wambach G, Helber A. Na-K-ATPase in erythrocyte ghosts is not a marker for primary hypertension.Clin Exp Hypertens 1981;3:663–673.

    Google Scholar 

  73. Garay RP, Elghozi JL, Dagher C, et al. Laboratory distinction between essential and secondary hypertension by measurement of erythrocyte cation fluxes.N Engl J Med 1980;302:769–771.

    Google Scholar 

  74. Wambach G, Helber A, Bonner G, et al. Natrium-kalium ATPase Aktivität in Erythrozytenghosts von Patienten mit essentieller Hypertonie.Klin Wochenschr 1979;57:169–172.

    Google Scholar 

  75. Woods KL, Beevers DG, West MJ. Racial differences in red cell cation transport and their relationship to essential hypertension.Clin Exp Hypertens 1981;3:655–662.

    Google Scholar 

  76. Rygielski DB, Kropp DZ, Duran NN. Hypertension and the Na-K pump (abstract).Fed Proc 1981;40:611.

    Google Scholar 

  77. Walter U, Distler A. Effects of ouabain and furosemide on ATPase activity and sodium transport in erythrocytes of normotensives and of patients with essential hypertension. In: Zumkley H, Losse H, eds.Intracellular Electrolytes and Arterial Hypertension. Stuttgart: Georg Thieme Verlag, 1980: 170–181.

    Google Scholar 

  78. Forrester TE, Alleyne GAO. Leucocyte electrolytes and sodium efflux rate constants in the hypertension of preeclampsia.Clin Sci 1980;59:199s-201s.

    Google Scholar 

  79. Poston L, Sewell RB, Wilkinson SP, et al. Evidence for a circulating sodium transport inhibitor in essential hypertension.Br Med J 1981;282:847–849.

    Google Scholar 

  80. Thomas RD, Edmondson RPS, Hilton PJ, et al. Abnormal sodium transport in leucocytes from patients with essential hypertension and the effect of treatment.Clin Sci Mol Med 1975;48:169s-170s.

    Google Scholar 

  81. De Wardener HE, McGregor CA. Dahl's hypothesis that a saluretic substance may be responsible for a sustained rise in arterial pressure: Its possible role in essential hypertension.Kidney Int 1980;18:1–9.

    Google Scholar 

  82. De Mendonca M, Grichois ML, Garay RP, et al. Abnormal net Na+ and K+ fluxes in erythrocytes of three varieties of genetically hypertensive rats.Proc Natl Acad Sci USA 1980;77:4283–4286.

    Google Scholar 

  83. Cusi D, Barlassina C, Ferrandi M, et al. Relationship between altered Na+,K+-countertransport in the erythrocytes of essential hypertensive patients.Clin Sci 1981;61:335–345.

    Google Scholar 

  84. Garay RP, Dagher G, Pernollet MG, et al. Inherited defect in Na+,K+-cotransport system in erythrocytes from essential hypertensive patients.Nature 1980;284:281–283.

    Google Scholar 

  85. Davidson J, Opie L, Keding B. Sodium-potassium cotransport activity as genetic marker in essential hypertension.Br Med J 1982;284:539–541.

    Google Scholar 

  86. Stessman J, Melker J, Sharon R, et al. Erythrocyte Na+,K+ cotransport and blood pressure in idential twins.Clin Exp Hypertens 1983;A5:493–499.

    Google Scholar 

  87. Weder AB, Torretti BA, Julius S. Racial differences in erythrocyte cation transport.Hypertension 1984;6:115–123.

    Google Scholar 

  88. Bianchi G, Ferrari P, Trizio D, et al. Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link.Hypertension 1985;7:319–325.

    Google Scholar 

  89. Adragna NC, Canessa ML, Solomon H, et al. Red cell lithium sodium countertransport and cotransport in patients with essential hypertension.Hypertension 1982;4:795–804.

    Google Scholar 

  90. Canessa M, Spalvins A, Adragna N, et al. Red cell sodium countertransport and cotransport in normotensive and hypertensive blacks.Hypertension 1984;6:344–351.

    Google Scholar 

  91. Smith JB, Ash KO, Hunt SC, et al. Three red cell sodium transport systems in hypertensive and normotensive Utah adults.Hypertension 1984;6:159–166.

    Google Scholar 

  92. Garay RP, Nazaret C, Dagher G, et al. A genetic approach to the geography of hypertension: Examination of Na+,K+ cotransport in Ivory Coast Africans.Clin Exp Hypertens 1981;3:861–870.

    Google Scholar 

  93. M'Buyamba-Kabangu JR, Lijnen P, Groeseneken D, et al. Racial differences in intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of normal male subjects.J Hypertens 1984;2:647–651.

    Google Scholar 

  94. Mahnensmith RL, Aronson PS. The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathological processes.Circ Res 1985;56:773–788.

    Google Scholar 

  95. Weder AB. Red cell lithium-sodium countertransport and renal lithium clearance in hypertension.N Engl J Med 1986;314:198–201.

    Google Scholar 

  96. Lijnen P, M'Buyamba-Kabangu JR, Fagard R, et al. Intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of white normal male subjects with and without a family history of hypertension.J Hypertens 1984;2:25–30.

    Google Scholar 

  97. Aviv A. The lymphocyte Na+/H+ antiport and its activation by increased NaCl intake: The link with salt sensitivity and cellular Ca+2 regulation.Eur J Clin Invest 1994;24:525–528.

    Google Scholar 

  98. Rosskopf D, Düsing R, Siffert W. Membrane sodium-proton exchange and primary hypertension.Hypertension 1993;21:607–617.

    Google Scholar 

  99. Hennessey JF, Ober KP. Racial difference in intact erythrocyte ion transport.Ann Clin Lab Sci 1982;12:35–41.

    Google Scholar 

  100. Simon G. Is intracellular sodium increased in hypertension?Clin Sci 1989;76:455–461.

    Google Scholar 

  101. Carr SJ, Thomas TH. Perturbation of blood cell and platelet membranes in human essential hypertension. In: Swales JD, ed.Textbook of Hypertension. Oxford: Blackwell Scientific Publications, 1994: 160–174.

    Google Scholar 

  102. Simon G, Conklin DJ. In vivo erythrocyte sodium concentration in human hypertension is reduced, not increased.J Hypertens 1986;4:71–75.

    Google Scholar 

  103. Lijnen P, Groeseneken D, Laermans M, et al. Methodological assessment of assays for intracellular concentrations and transmembrane fluxes of sodium and potassium in erythrocytes of man.Methods Find Exp Clin Pharmacol 1984;6:293–301.

    Google Scholar 

  104. Lijnen P, Hespel P, Lommelen G, et al. Intracellular sodium, potassium and magnesium concentration, ouabainsensitive86rubidium-uptake and sodium efflux and Na+, K+-cotransport activity in erythrocytes of normal male subjects studied on two occasions.Methods Find Exp Clin Pharmacol 1986;8:525–533.

    Google Scholar 

  105. Postnov YV. An approach to the explanation of cell membrane alteration in primary hypertension.Hypertension 1990;15:332–337.

    Google Scholar 

  106. Aalkjaer C, Heagerty AM, Parvin SD, et al. Cell membrane sodium transport: A correlation between human resistance vessels and leucocytes.Lancet 1986;1:649–651.

    Google Scholar 

  107. Swales JD. Functional disturbance of the cell membrane in hypertension.J Hypertens 1990;8(Suppl 7):203–211

    Google Scholar 

  108. Jelicks LA, Gupta RK. NMR measurement of free calcium, free magnesium and intracellular sodium in the aorta of the normal and spontaneously hypertensive rat.J Biol Chem 1990;265:1394–1400.

    Google Scholar 

  109. Bukowski RD. Intracellular Ca2+ metabolism of isolated resistance arteries and cultured vascular myosites of spontaneously hypertensive and Wistar-Kyoto normotensive rats.J Hypertens 1990;8:37–43.

    Google Scholar 

  110. Balfe JW, Cole C, Smith EKM, et al. A hereditary sodium transport defect in the human red blood cell.J Clin Invest 1968;47:4a.

    Google Scholar 

  111. Love W, Burch GE. Plasma and erythrocyte sodium and potassium concentration in a group of southern white and negro blood donors.J Lab Clin Med 1953;41:258–267.

    Google Scholar 

  112. Munro-Faure AD, Hill DM, Anderson J. Ethnic differences in human blood cell sodium concentration.Nature 1971;231:457–458.

    Google Scholar 

  113. Lasker N, Hopp L, Grossman S, et al. Race and sex differences in erythrocyte Na+,K+, and Na+,K+-adenosine triphosphatase.J Clin Invest 1985;75:1813–1820.

    Google Scholar 

  114. McGregor GA, Fenton S, Zadeh JA, et al. An increase in a circulating inhibitor of Na+,K+-dependent ATPase: A possible link between salt intake and the development of essential hypertension.Clin Sci 1981;61:17s-20s.

    Google Scholar 

  115. Brewer GJ. Genetic and population studies of quantitative levels of adenosine triphosphate in human erythrocytes.Biochem Genet 1967;1:25–34.

    Google Scholar 

  116. Woods JW, Falk RJ, Pittman AW, et al. Increased red cell sodium lithium countertransport in normotensive sons of hypertensive parents.N Engl J Med 1982;306:593–595.

    Google Scholar 

  117. Gudmundsson O, Andersson O, Herlitz H, et al. Blood pressure, intraerythrocyte content and transmembrane fluxes of sodium during normal and high salt intake in subjects with and without a family history of hypertension.J Hypertens 1984;6:S35-S41.

    Google Scholar 

  118. Henningsen NC, Nelson D. Red cell metabolism of sodium in relatives to patients with an established essential hypertension. In: Losse H, Zumkley H, eds.Intracellular Electrolytes and Arterial Hypertension. Stuttgart: Georg Thieme Verlag, 1980;205–212.

    Google Scholar 

  119. Zidek W, Vetter H, Dorst KG, et al. Intracellular Na2+ and Ca2+ activities in essential hypertension.Clin Sci 1982;63:41S-44S.

    Google Scholar 

  120. Heagerty AM, Milner M, Bing RF, et al. Leucocyte membrane sodium transport in normotensive populations: Dissociation of abnormalities of sodium efflux from raised blood pressure.Lancet 1982;2:894–896.

    Google Scholar 

  121. Pedersen KE, Nielson JR, Kjaer K, et al. Na+ influx in lymphocytes from normotensive subjects with and without a family history of essential hypertension.J Hypertens 1983;1:132S-134s.

    Google Scholar 

  122. Krzesinski JM. Contribution à l'étio-athogénie de l'hypertension artérielle essentielle par la mesure des flux de sodium et potassium érythrocytaires. Mémoire, Université de Liège, 1985.

  123. M'Buyamba-Kabangu JR, Lijnen P, Fagard R, et al. Intracellular concentration and transmembrane fluxes of sodium and potassium in erythrocytes of normal men and women.Arch Gynecol 1985;236:219–224.

    Google Scholar 

  124. M'Buyamba-Kabangu JR, Lijnen P, Fagard R, et al. Erythrocyte concentrations and transmembrane fluxes of sodium and potassium and biochemical measurements during the menstrual cycle in normal women.Am J Obstet Gynecol 1985;151:687–693.

    Google Scholar 

  125. Englehardt I, Schlolze J, Frille J, et al. Ouabain-insensitive net sodium influx in erythrocytes in health and disease. Submitted for publication 1995.

  126. Beilin LJ, Knight GJ, Munro-Faure AD, et al. The sodium, potassium and water contents of red blood cells of healthy human adults.J Clin Invest 1966;45:1817–1825.

    Google Scholar 

  127. Stokes GS, Monaghan JC, Marwood JF. Erythrocyte cation transport is sex-related and is modified by oral contraceptives.Clin Exp Hypertens 1985;A7:1199–1215.

    Google Scholar 

  128. Sigström L, Waldenström J, Karlberg P. Characteristics of active sodium and potassium transport in erythrocytes of healthy infants and children.Acta Paediatr Scand 1981;70:347–352.

    Google Scholar 

  129. Beutler E, Kuhl N, Sachs P. Sodium-potassium-ATPase activity is influenced by ethnic origin and not by obesity.N Engl J Med 1983;309:756–760.

    Google Scholar 

  130. Lijnen P, M'Buyamba-Kabangu JR, Fiocchi R, et al. Sodium and potassium fluxes and concentrations in erythrocytes of normal subjects during prolonged sodium depletion and repletion.Postgrad Med J 1986;62:3–12.

    Google Scholar 

  131. Trevisan M, Cooper R, Ostrow D, et al. Dietary sodium, erythrocyte sodium concentration, sodium-stimulated lithium efflux and blood pressure.Clin Sci 1981;61:29s-32s.

    Google Scholar 

  132. Cooper R, Trevisan M, Van Horn L, et al. Effect of dietary sodium reduction on red blood cell sodium concentration and sodium-lithium countertransport.Hypertension 1984;6:731–735.

    Google Scholar 

  133. Morgan T, Myers J, Fitzgibbon W. Sodium intake, blood pressure and red cell sodium efflux.Clip Exp Hypertens 1981;3:641–653.

    Google Scholar 

  134. Weissberg PL, West MJ, Wilkins MR, et al. Effects of changes in dietary sodium intake on normotensive subjects with and without a genetic predisposition to essential hypertension.J Hypertens 1984;2:511s-513s.

    Google Scholar 

  135. Doucet A. Na-K-ATPase: General considerations, role and regulation in the kidney.Adv Nephrol 1985;14:87–159.

    Google Scholar 

  136. Kanazawa T, Saito M, Tonomura Y. Formation and decomposition of a phosphorylated intermediate in the reaction of Na plus-K plus dependent ATPase.J Biochem 1970;67:693–711.

    Google Scholar 

  137. Robinson JD, Flashner MS. Cation and nucleotide interactions with the Na,K-ATPase. In: Skou JC, Norby JG, eds.Na,K-ATPase. Structure and Kinetics. London: Academic Press, 1979:275–285.

    Google Scholar 

  138. Kojima I, Yoshihara S, Ogata E. Involvement of digitalislike substance in genesis of deoxycorticosterone-salt hypertension.Life Sci 1982;30:1775–1781.

    Google Scholar 

  139. Price MB, Pamnani MB, Burris, JF, et al. Acute volume expansion in humans releases a factor which inhibits the vascular Na+,K+ pump.J Hypertens 1984;2(Suppl 3):471–472.

    Google Scholar 

  140. Dagher G, Brossard M, Feray JC, et al. Modulation of erythrocyte Na transport pathway(s) by excess Na intake.Life Sci 1985;37:243–253.

    Google Scholar 

  141. Beuckelmann D, Erdmann E. Perturbation of sodiumlithium countertransport in red cells.N Engl J Med 1985;312:193–1194.

    Google Scholar 

  142. Beilin LJ. The Fifth Sir George Pickering Lecture. Epitaph to essential hypertension—a preventable disorder of known etiology?J Hypertens 1988;6:85–94.

    Google Scholar 

  143. Genest J, Lemieux G, Savignon A, et al. Human arterial hypertension: A state of mild chronic hyperaldosteronism.Science 1956;123:503–505.

    Google Scholar 

  144. Bianchi G, Cusi D, Gatti M, et al. A renal abnormality as a possible cause of essential hypertension.Lancet 1979;1:173–177.

    Google Scholar 

  145. Bianchi G, Ferrari P, Cusi D, et al. Genetic hypertension and the kidney.J Cardiovasc Pharmacol 1984;6(Suppl 1):S162-S170.

    Google Scholar 

  146. Esler M, Julius S, Zweifler A, et al. Mild high renin essential hypertension: Neurogenic human hypertension.N Engl J Med 1977;297:405–411.

    Google Scholar 

  147. Postnov YV, Orlov SN. Alteration of cell membranes in primary hypertension. In:Hypertension, Physiopathology and treatment. New York: McGraw-Hill, 1983.

    Google Scholar 

  148. Meyer P, Garay RP, Mendonca M. Ion transport system in hypertension. In:Hypertension, Physiopathology and Treatment. New York: McGraw-Hill, 1983.

    Google Scholar 

  149. Berglund G, Wikstrand J, Wallentin I, et al. Sodium excretion and sympathetic activity in relation to severity of hypertension.Lancet 1976;1:325–328.

    Google Scholar 

  150. Kesteloot H, Vuylsteke M, Costenoble A. Relationship between blood pressure and sodium and potassium intake in a Belgian male population group. In: Kesteloot H, Joossens JV, eds.Epidemiology of Arterial Blood Pressure. Martinus Nijhoff, 1980:345.

  151. M'Buyamba-Kabangu JR, Staessen J, Fagard R, et al. Blood pressure and urinary cations in urban bantu of Zaïre.Am J Epidemiol 1986;124:957–968.

    Google Scholar 

  152. Shibata, Hatano S. A salt restriction trial in Japan. In: Gross F, Strasser T, eds.Mild Hypertension, Natural History and Management. London: Pitman Medical, 1979: 147.

    Google Scholar 

  153. McGregor GA. Sodium is more important than calcium in essential hypertension.Hypertension 1985;7:628–640.

    Google Scholar 

  154. Joossens JV, Claessen J, Geboers J, Claes JH. Electrolytes and creatinine in multiple 24 hour collections (1970–1974). In: Kestleloot H, Joossens JV, eds.Epidemiology of Arterial Blood Pressure. Amsterdam: Martinus Nijhoff, 1980:45.

    Google Scholar 

  155. Simpson FO. Blood pressure and sodium intake. In: Bulpitt CJ, ed.Handbook of Hypertension, Vol. 6, Epidemiology of Hypertension. Amsterdam: Elsevier Science, 1985:175.

    Google Scholar 

  156. Gleiberman L. Blood pressure and dietary salt in human populations.Ecol Food Nutr 1973;2:143–149.

    Google Scholar 

  157. Intersalt Cooperative Research Group. Intersalt: An international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion.Br Med J 1988;297:319–328.

    Google Scholar 

  158. Mtabaji JP, Nara Y, Yamori Y. The cardiac study in Tanzania: Salt intake in the causation and treatment of hypertension.J Hum Hypertens 1990;4:80–81.

    Google Scholar 

  159. Dahl LK, Heine M, Tassinari L. Effects of chronic excess salt ingestion. Evidence that genetic factors play an important role in susceptible to experimental hypertension.J Exp Med 1962;115:1173–1190.

    Google Scholar 

  160. Shaper AG, Leonard PJ, Jones KW. Environmental effects on body build, blood pressure and blood chemistry of nomadic warriors serving the army of Kenya.East Afr Med J 1969;46:282–289.

    Google Scholar 

  161. Sever PS, Poulter NR. An hypothesis for the pathogenesis of essential hypertension, based on a new human model of migration induced blood pressure. In: Hofman A, Grobbee DE, Schalekamp MADH, eds.The Early Pathogenesis of Hypertension. Amsterdam: Excerpta Medica, 1987:127.

    Google Scholar 

  162. McGregor GA, Markandu N, Best F, et al. Double-blind randomized cross-over trial of moderate sodium restriction in essential hypertension.Lancet 1982;1:351–355.

    Google Scholar 

  163. Parijs J, Joossens JV, Van Der Linden LV, et al. Moderate sodium restriction and diuretics in the treatment of hypertension.Am Heart J 1973;85:22–34.

    Google Scholar 

  164. Kempner W. Treatment of hypertensive vascular disease with rice diet.Am J Med 1948;4:545–577.

    Google Scholar 

  165. Haddy FJ. Digitalis-like circulating factor in hypertension, potential messenger between salt balance and intracellular sodium.Cardiovasc Drugs Ther 1990;4(Suppl 2):343–349.

    Google Scholar 

  166. Gerber JG, Nies AS. Pharmacology of antihypertensive drugs. In: Genest J, Kuhl O, Hamet P, et al., eds.Hypertension. New York: McGraw-Hill, 1983:1093.

    Google Scholar 

  167. Winer BM. Antihypertensive mechanisms of salt depletion induced by hydrochlorothiazide.Circulation 1961;24:788–796.

    Google Scholar 

  168. Meyers J, Morgan T. The effect of sodium intake on the blood pressure related to age and sex.Clin Exp Hypertens 1983;(A)5:99–118.

    Google Scholar 

  169. Luft FC, Grim CE, Fineberg, Weinberg MC. Effects of volume expansion and contraction in normotensive blacks, whites and subjects of different ages.Circulation 1979;59:643–650.

    Google Scholar 

  170. Parker JC, Bukowitz LR. Physiologically instructive genetic variants involving the human red cell membrane.Physiol Rev 1983;63:261–313.

    Google Scholar 

  171. Cooper R, Trevisan M, Ostrow D, et al. Blood pressure and sodium-lithium countertransport: Findings in population based surveys.J Hypertens 1984;2:467–471.

    Google Scholar 

  172. Swales JD. Interpreting ion transport studies in hypertension: Methods, myths and hypothesis.J Hypertens 1983;1(Suppl 2):391.

    Google Scholar 

  173. McDonald AM, Dyer AR, Liu K, et al. Sodium-lithium countertransport and blood pressure control by nutritional intervention in mild hypertension.J Hypertens 1988;6;283–291.

    Google Scholar 

  174. Hespel P, Lijnen P, Fiocchi R, et al. Cationic concentrations and transmembrane fluxes in erythrocytes of humans during exercise.J Appl Physiol 1986;61:37–43.

    Google Scholar 

  175. Hespel P, Lijnen P, Fagard R, et al. Change in erythrocyte sodium and plasma lipids associated with physical training.J Hypertens 1988;6:159–166.

    Google Scholar 

  176. Hunt SC, Williams RR, Ash KO. Changes in sodiumlithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah.Cardiovasc Drugs Ther 1990;4(Suppl 2):357S-362S.

    Google Scholar 

  177. Jones AW. Altered ion transport in vascular smooth muscle from spontaneously hypertensive rats: Influence of aldosterone, norepinephrine and angiotensin.Circ Res 1973;33:563–572.

    Google Scholar 

  178. Furspan PB, Bohr DF. Lymphocyte abnormalities in three types of hypertension in the rat.Hypertension 1985;7: 860–866.

    Google Scholar 

  179. Furspan PB, Bohr DF. Calcium related abnormalities in lymphocytes from genetically hypertensive rats.Hypertension 1986:8(Suppl II):123–126.

    Google Scholar 

  180. Van Breemen C, Cauvin C, Johns A, et al. Ca2+ regulation of vascular smooth muscle.Fed Proc 1986;45:2746–2751.

    Google Scholar 

  181. Livine A, Bolfe JW, Veitch R, et al. Increased platelet Na-H exchange rates in essential hypertension. Application of a novel test.Lancet 1987;40:533–536.

    Google Scholar 

  182. Beck BC, Vallega G, Muslin AJ, et al. Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+-H+ exchange.J Clin Invest 1989;83:822–829.

    Google Scholar 

  183. David-Dufilho M, Pernollet MG, Sang HL, et al. Active Na+ and Ca2+ transport, Na+-Ca2+ exchange and intracellular Na+ and Ca2+ content in young spontaneously hypertensive rats.J Cardiovasc Pharmacol 1986;8(Suppl 8):130–135.

    Google Scholar 

  184. Webb C, Bohr DF. Potassium relaxation of vascular smooth muscle from spontaneously hypertensive rats.Blood Vessels 1979;16:71–79.

    Google Scholar 

  185. Orlov SN, Pokudin NI, Postnov YV. Calmodulin-dependent Ca-transport in erythrocytes of spontaneously hypertensive rats.Pflügers Arch 1983;397:54–56.

    Google Scholar 

  186. Adeaya SA, Norma RI, Bing RF. Erythrocyte membrane calcium adenosine-5′-triphosphate activity in the spontaneously hypertensive rat.Clin Sci 1989;77:395–400.

    Google Scholar 

  187. Dominiczak AF, Bohr DF. Cell membrane abnormalities and the regulation of intracellular calcium concentration in hypertension.Clin Sci 1990;79:415–423.

    Google Scholar 

  188. Dominiczak AF, Lazar DF, Das AK, Borh DF. Lipid bilayer in genetic hypertension.Hypertension 1991;18:748–757.

    Google Scholar 

  189. Swales JD. Functional disturbance of the cell membrane in hypertension.J Hypertens 1990;8(Suppl 7):203–211.

    Google Scholar 

  190. Cooper RA. Abnormalities of cell membrane fluidity in the pathogenesis of disease.N Engl J Med 1977;297:371–377.

    Google Scholar 

  191. Kimmelberg HK. Alterations in phospholipid dependent (Na-K) ATPase activity due to lipid fluidity.Biochim Biophys Acta 1975;413:143–146.

    Google Scholar 

  192. Grisham CM, Barnett RE. The effects of long-chain alcohols on membrane lipids and the (Na-K) ATPase.Biochim Biophys Acta 1973;411:417–422.

    Google Scholar 

  193. Wiley JS, Cooper RA. Inhibition of cation transport by cholesterol enrichment of human red cell membranes.Biochim Biophys Acta 1975;413:425–431.

    Google Scholar 

  194. Jackson PA, Morgan DB. The relation between membrane cholesterol and phospholipid and sodium efflux in erythrocytes from healthy subjects and patients with chronic cholestasis.Clin Sci 1982;62:101–107.

    Google Scholar 

  195. Lijnen P, Fagard R, Staessen J, et al. Erythrocyte membrane lipids and cationic transport systems in men.J Hypertens 1992;10:1205–1211.

    Google Scholar 

  196. Lijnen P, Fenyvesi A, Bex M, et al. Erythrocyte cation transport systems and membrane lipids in insulindependent diabetics.Am J Hypertens 1993;6:763–770.

    Google Scholar 

  197. Lijnen P, Celis P, Fagard R, et al. Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems.J Hypertens 1994;12:59–64.

    Google Scholar 

  198. Bing RF, Booth GC, Heagerty AM, Swales JD. Erythrocyte membrane calcium binding in normotensive and hypertensive subjects.J Hypertens 1986;4(Suppl 6):299s-302s.

    Google Scholar 

  199. Vincenzi FF, Morris CD, Kinsel LB, et al. Decreased calcium pump adenosine triphosphate in red blood cells of hypertensive subjects.Hypertension 1986;8:1058–1066.

    Google Scholar 

  200. Touyz RM, Milne FJ, Reinach SG: Platelet and erythrocyte Mg2+, Ca2+, Na+, K+ and cell membrane adenosine triphosphatase activity in essential hypertension in blacks.J Hypertens 1992;10:571–578.

    Google Scholar 

  201. Postnov YV, Orlov SN, Reznikova MB, et al. Calmodulin distribution and Ca2+ transport in the erythrocyte of patients with essential hypertension.Clin Sci 1984;66:459–463.

    Google Scholar 

  202. Bruschi G, Bruschi MC, Caroppo M, et al. Cytoplasmicfree (Ca2+) is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients.Clin Sci 1985;68:179–184.

    Google Scholar 

  203. Erne P, Bolli P, Burgisser E, Buhler F. Correlation of platelet calcium with blood pressure: Effect of antihypertensive therapy.N Engl J Med 1984;310:1084–1088.

    Google Scholar 

  204. Bing RF, Heagerty AM, Jackson JA, et al. Leucocyte ionized calcium and sodium content and blood pressure in humans.Hypertension 1986;8:483–488.

    Google Scholar 

  205. Resink TJ, Tkachuk VA, Erne P, Buhler FR. Platelet membrane calmodulin-stimulated calcium adenosine triphosphate: Altered activity in essential hypertension.Hypertension 1986;8:159–166.

    Google Scholar 

  206. Resnick LM, Gupta RK, Soza KE, et al. Intracellular pH in human and experimental hypertension.Proc Natl Acad Sci USA 1987;84:7663–7667.

    Google Scholar 

  207. Tobian L, Janecek A, Tomboulian A, Ferreira D. Sodium and potassium in the walls of the arterioles in experimental renal hypertension.J Clin Invest 1961;40:1922–1925.

    Google Scholar 

  208. Swales JD. Membrane transport of ions in hypertension.Cardiovasc Drugs Ther 1990;4(Suppl 2):367–372.

    Google Scholar 

  209. Blaustein MP, Hamlyn JM. Sodium transport inhibition, cell calcium and hypertension; the natriuretic hormone /Na+-Ca2+ exchange/hypertension hypothesis.Am J Med 1984;77:45–59.

    Google Scholar 

  210. Blaustein MP. Sodium ions, calcium ions, blood pressure regulation and hypertension, a reassessment and a hypothesis.Am J Physiol 1977;232:C165-C173.

    Google Scholar 

  211. Bianchi G, Ferrari P. Animal models for arterial hypertension. In: Genest G, Kuchel O, Hamet P, eds.Hypertension. New York: McGraw-Hill, 1983:534.

    Google Scholar 

  212. Curtis JJ, Luke RG, Dustan HP, et al. Remission of essential hypertension after renal transplantation.N Engl J Med 1983;309:1009–1015.

    Google Scholar 

  213. Skrabal F, Herholz H, Neumayr M, et al. Salt sensitivity in humans is linked to enhanced sympathetic responsiveness and to enhanced proximal tubular reabsorption.Hypertension 1984;6:152–158.

    Google Scholar 

  214. Brenner RM, Garcia DL, Anderson S. Glomerule and blood pressure.Am J Hypertens 1988;1:335–347.

    Google Scholar 

  215. Haddy FJ. Ionic control of vascular smooth muscle cells.Kidney Int 1988;25(Suppl):S2-S8.

    Google Scholar 

  216. Hamlyn JM, Ringel R, Schaeffer H, et al. A circulating inhibitor, of (Na+, K+) ATPase associated with essential hypertension.Nature 1982;300:650–652.

    Google Scholar 

  217. De Wardener HE, McGregor GA, Clarkson EM, et al. Effect of sodium intake on ability of human plasma to inhibit renal Na+, K+-adenosine triphosphate in vitro.Lancet 1981;1:411–413.

    Google Scholar 

  218. Hasegawa T, Masugi F, Ogihara T, Kumahara Y. Increase in plasma ouabain-like inhibitor of Na+, K+-ATPase with high sodium intake in patients with essential hypertension.J Clin Hypertens 1987;3:419–423.

    Google Scholar 

  219. Quintanilla AP, Wagener OE. Diuretics and cation in hypertensive blacks.Cardiovasc Drugs Ther 1990;4:383–387.

    Google Scholar 

  220. Haupert GT, Sancho JM. Sodium transport inhibitor in bovine hypothalamus.Proc Natl Acad Sci USA 1979;76:4658–4660.

    Google Scholar 

  221. De Wardener HE, Clarkson EM. Concept of natriuretic hormone.Physiol Rev 1985;654:658–759.

    Google Scholar 

  222. Morgan K, Lewis MD, Spurlock G, et al. Characterization and partial purification of the sodium, potassium-ATPase inhibitor released from cultured hypothalamic cell.J Biol Chem 1985;260:13595–13600.

    Google Scholar 

  223. Haddy FJ. Digitalis-like circulating factor in hypertension: Potential messenger between salt balance and intracellular sodium.Cardiovasc Drugs Ther 1990;4(Suppl 2):343–349.

    Google Scholar 

  224. Bova S, Blaustein MP, Ludens JH, et al. Effects of an endogenous ouabain-like compound on heart and aorta.Hypertension 1991;17:944–950.

    Google Scholar 

  225. Nabel EG, Berk BC, Brock TA, Swith L. Na-Ca exchange in cultured vascular smooth muscle cells.Circ Res 1988;62:486–493.

    Google Scholar 

  226. Smith JB, Grago EJ Jr, Smith L. Na+/Ca2+-antiport in arterial smooth muscle cells: Inhibition by magnesium and other divalent cations.J Biol Chem 1987;262:11988–11994.

    Google Scholar 

  227. Mulvany MJ. Changes in sodium pump activity and vascular contraction.J Hypertens 1985;3:429–436.

    Google Scholar 

  228. Van Breemen C, Daronson P, Lomt Zenheiser R. Sodium-calcium interaction in mammalian smooth muscle.Pharm Rev 1979;3:167–174.

    Google Scholar 

  229. Harder DR, Hermesmeyer K. Membrane mechanism in arterial hypertension.Hypertension 1983;5:404–408.

    Google Scholar 

  230. Aalkjaer C, Heagerty AM, Petersen KK, et al. Evidence for increased media thickness and increased neuronal amine uptake, but depressed excitation contraction coupling in isolated resistance vessels from essential hypertension.Circ Res 1987;61:181–186.

    Google Scholar 

  231. Aalkjaer C, Heagerty AM, Barley I, et al. Studies of isolated resistance vessels from offspring of essential hypertensive patients.Hypertension 1987;9(Suppl III):155–158.

    Google Scholar 

  232. Berk BC, Alexander RW, Brock TA, et al. Vasoconstriction, a new activity for platelet-derived growth factor.Science 1986;232:87–90.

    Google Scholar 

  233. Berk BL, Gordon HM, Vekhstein V, et al. Angiotensin II stimulates protein synthesis in vascular smooth muscle independent of C-fos.Clin Res 1988;36:425A.

    Google Scholar 

  234. Berk BC, Brock TA, Gimbrone MA Jr, Alexander RW. Early agonist-mediated ionic events in cultured vascular smooth muscle cells.J Biol Chem 1987;262:5065–5072.

    Google Scholar 

  235. Berk BC, Brock TA, Well RC, et al. Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction.J Clin Invest 1985;75:1083–1086.

    Google Scholar 

  236. Rozengurt E. Early signals in the mitogenic response.Science 1986;234:161–166.

    Google Scholar 

  237. L'Allemain G, Franchi A, Cragoe E Jr, Ponyssegur J. Blockade of the Na+/H+-antiport abolishes growth factor induced DNA synthesis in fibroblasts.J Biol Chem 1984;259:4313–4319.

    Google Scholar 

  238. Lever AF. Slow pressor mechanisms and smooth muscle mitogens in hypertension.J Clin Hypertens 1987;3:323–327.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Belgium

    Paul Lijnen

Authors
  1. Paul Lijnen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lijnen, P. Alterations in sodium metabolism as an etiological model for hypertension. Cardiovasc Drug Ther 9, 377–399 (1995). https://doi.org/10.1007/BF00879027

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00879027

Key Words

Search

Navigation