Skip to main content
SpringerLink
Log in

Hypertension

  • Chapter
Red Cell Membrane Transport in Health and Disease

Abstract

In 1973, Jones presented data on increased 42K and 36Cl turnover in aortic strips from spontaneously hypertensive rats (SHR) developed by Okamoto and Aoki as an experimental model of human primary or essential hypertension. These results raised at least 2 questions. First, are these abnormalities caused by altered permeability of plasma membrane for monovalent ions? Second, are these abnormalities linked to the pathogenesis of primary hypertension, or are they a consequence of long-term blood pressure elevation? The complex pattern of monovalent ion com-partmentalisation in extra- and intracellular spaces complicated the use of aortic strips for analysis of the first issue. Because cell culture techniques had not been developed at that time, we decided to design an appropriate methodological approach involving erythrocytes. Erythrocytes from SHR, normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats were randomly investigated in our pilot experiments. To our surprise, we observed that the rate of 22Na efflux was increased in SHR compared to normotensive rats (Postnov et al. 1975). In the next 2 decades, a dozen laboratories were engaged in the further characterisation of ion transport across the plasma membrane in primary hypertension.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adragna NC, Canessa ML, Solomon H, Slater E, Tosteson DC (1982) Red cell lithium-sodium countertransport and sodium-potassium cotransport in patients with essential hypertension. Hypertension 4:795–804

    Article  Google Scholar 

  • Alonso A, Arrazola A, Garciandia A, Esparza N, Gomez-Alamillo C, Diez J (1993) Erythrocyte anion exchanger activity and intracellular pH in essential hypertension. Hypertension 22:348–356

    Article  Google Scholar 

  • Alvarez-Guerra M, Nazaret C, Garay RP (1998) The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats. J Hypertens 16:1499–1504

    Article  Google Scholar 

  • Aronson PS (1982) Red-cell sodium-lithium countertransport and essential hypertension. N Engl J Med 307:317

    Google Scholar 

  • Bianchi G, Ferrari P, Trizio D, Ferrandi M, Torielli L, Barber BR, Polli E (1985) Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link. Hypertension 7:319–325

    Google Scholar 

  • Bianchi G, Tripodi G, Casari G, Salardi S, Barber BR, Garcia R, Leoni P, Torielli L, Cusi D, Ferrandi M (1994) Two point mutations within the adducin genes are involved in blood pressure variation. Proc Natl Acad Sci USA 91:3999–4003

    Article  ADS  Google Scholar 

  • Cacciafesta M, Ferri C, Carlomagno A, De Angelis C, Scuteri A, Guidoni L, Luciani AM, Rosi A, Viti V, Santucci A (1994) Erythrocyte Na-K-Cl cotransport activity in low renin essential hypertensive patients. A 23Na nuclear magnetic resonance study. Am J Hypertens 7:151–158

    Google Scholar 

  • Canessa ML (1989) The Na-K-Cl cotransport in essential hypertension: cellular functions and genetic environment interactions. Int J Cardiol 25, suppl L.S37–S45

    Google Scholar 

  • Canessa M, Adragna N, Solomon HS, Connolly TM, Tosteson DC (1980) Increased sodium-lithium counter-transport in red cells of patients with essential hypertension. N Engl J Med 302:772–776

    Article  Google Scholar 

  • Canessa M, Bize I, Spalvins A, Falkner B, Katz S (1986) Na-K-Cl cotransport and Na pump in red cells of young blacks and blood pressure response to salt loading. J Clin Hypertens 2:101–108

    Google Scholar 

  • Canessa M, Morgan K, Goldszer R, Moore TJ, Spalvins A (1991) Kinetics abnormalities of the red blood cell sodium-proton exchange in hypertensive patients. Hypertension 17:340–348

    Article  Google Scholar 

  • Canessa M, Romero JR, Ruiz-Opazo N, Herrera VL (1993) The alpha 1 Na+-K+ pump of the Dahl salt-sensitive rat exhibits altered Na+ modulation of K+ transport in red blood cells. J Membrane Biol 134:107–122

    Article  Google Scholar 

  • Cusi D, Fossali E, Piazza A, Tripodi G, Barlassina C, Dozzoli E, Vezzoli G, Stella P, Soldati L, Bianchi G (1991) Heritability estimate of erythrocyte Na-K-Cl cotransport in normotensive and hypertensive families. Am J Hypertens 4:725–754

    Google Scholar 

  • Davis JPL, Chipperfield AR, Harper AA (1993) Accumulation of intracellular chloride by (Na-K-Cl) cotransport in rat arterial muscle is enhanced in deoxycorticosterone acetate (DOCA)/salt hypertension. J Mol Cell Cardiol 25:233–237

    Article  Google Scholar 

  • De la Sierra, Coca A, Aguilera MT, Ingelmo M, Urbano-Marquez A (1989) Clinical profiles and erythrocyte Na+ transport abnormalities of four major types of primary hypertension in Spain. Kidney Int 36:114–119

    Article  Google Scholar 

  • De Mendonca M, Knorr A, Grichois ML, Ben Ishay D, Garay RP, Meyer P (1982) Erythrocytic sodium ion transport systems in primary and secondary hypertension of the rat. Kidney Int, suppl 11 :S69–S75

    Google Scholar 

  • De Wardener HE (1996) Sodium transport inhibitors and hypertension. J Hypertens 14:S9–S18

    Google Scholar 

  • Delpire E, Lu J, England R, Dull C, Thorne T (1999) Deafness and imbalance associated with inactivation of the secretory Na-K-2C1 co-transporter. Nat Genet 22:192–195

    Article  Google Scholar 

  • Delva P, De Gasperi M, Degan M, Covi G, Lechi A (1985) Kinetics of bumetanide-sensitive Na+-K+ co-transport in erythrocytes of essential hypertensive patients. Clin Sci 69:607–611

    Google Scholar 

  • Delva P, Pastori C, Provoli E, Degan M, Arosio E, Montesi G, Steele A, Lechi A (1993) Erythrocyte Na+-H+ exchange activity in essential hypertensive and obese patients: role of excess body weight. J Hypertens 11:823–830

    Article  Google Scholar 

  • Delva P, Pastori C, Degan M, Montesi G, Lechi C, Steele A, Lechi A (1996) Erythrocyte Na+-H+ exchanger kinetics and Na+-Li+ countertransport activity in essential hypertensive patients. Eur J Clin Invest 26:64–70

    Article  Google Scholar 

  • Deng AY, Dene H, Rapp JP (1994) Mapping of a quantitative trait locus for blood pressure on rat chromosome 2. J Clin Invest 94:431–436

    Article  Google Scholar 

  • Ferrari P, Ferrandi M, Torielli L, Canessa M, Bianchi G (1987) Relationship between erythrocyte volume and sodium transport in the Milan hypertensive rat and age-dependent changes. J Hypertens 5:199–206

    Article  Google Scholar 

  • Ferrari P, Torielli L, Cirillo M, Salardi S, Bianchi G (1991) Sodium transport kinetics in erythrocytes and inside-out vesicles from Milan rats. J Hypertens 9:703–711

    Article  Google Scholar 

  • Ferrari P, Torielli L, Salardi S, Rizzo A, Bianchi G (1992) Na+/K+/Cl- cotransport in re-sealed ghosts from erythrocytes of the Milan hypertensive rats. Biochim Biophys Acta 1111:111–119

    Article  Google Scholar 

  • Flagella M, Clarke LL, Miller ML, Erway LC, Giannella RA, Andringa A, Gawenis LR, Kramer J, Duffy JJ, Doetschman T, Lorenz JN, Yamoah EN, Cardell EL, Shull GE (1999) Mice lacking the basolateral Na-K-2C1 cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J Biol Chem 274:26946–26955

    Article  Google Scholar 

  • Garay RP, Dagher G, Pernollet MG, Devynck MA, Meyer P (1980) Inherited defect in a Na+-K+ cotransport system in erythrocyte from essential hypertensive patients. Nature 284:281–283

    Article  ADS  Google Scholar 

  • Golovina VA, Blaustein MP (1997) Spatially and functionally distinct Ca2+ stores in sarcoplasmic and endoplasmic reticulum. Science 275:1643–1648

    Article  Google Scholar 

  • Gulak PV, Orlov SN, Pokudin NI, Postnov YV, Litvinov IS, Orlov NJ, Shnyrov VL (1984) Microcalorimetry and electrophoresis of the erythrocyte membrane of spontaneously hypertensive rats. J Hypertens 2:81–84

    Article  Google Scholar 

  • Gulak PV, Orlov SN, Postnov YV, Kiladze IS, Grigorian GL, Tabagua MI, Kajushin LP (1986) Investigation of membrane proteins in rat erythrocytes in spontaneous hypertension by means of spin-label technique. J Hypertens 4:313–317

    Article  Google Scholar 

  • Hamet P, Pausova Z, Adarichev S, Adaricheva K, Tremblay J (1998) Hypertension: genes and environment. J Hypertens 16:397–418

    Article  Google Scholar 

  • Hamlyn JM, Hamilton BP, Manunta P (1996) Endogenous ouabain, sodium balance and blood pressure: a review and a hypothesis. J Hypertens 14:151–167

    Article  Google Scholar 

  • Hardman TC, Lant AF (1996) Controversies surrounding erythrocyte sodium-lithium countertransport. J Hypertens 14:695–70

    Article  Google Scholar 

  • Harris EL, Kelly G, Barnard R (2000) Neither GH nor SS/JR rats have a A1079T transition in the α1Na+, K+-ATPase gene (abstract). Genetics of Experimental and Human Hypertension — Symposium of the International Society of Hypertension. Toledo, Ohio, USA, pp 19–20

    Google Scholar 

  • Herrera VLM, Ruiz-Opazo N (1990) Alteration of Na+, K+-ATPase 86Rb influx by a single amino acid substitution. Science 249:1023–1026

    Article  ADS  Google Scholar 

  • Huot SJ, Aronson PS (1991) Na+/H+ exchanger and its role in essential hypertension and diabetes mellitus. Diabetes Care 14:521–535

    Article  Google Scholar 

  • Imagawa M, Arakawa K (1986) Sodium-potassium cotransport in hypertension and hypotension. Japan Heart J 27:191–204

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Kaestner L, Bollensdorff C, Bernhardt I (1999) Non-selective voltage-activated cation channel in the human red blood cell membrane. Biochim Biophys Acta 1417:9–15

    Article  Google Scholar 

  • Kotelevtsev YV, Orlov SN, Pokudin NI, Agnaev VM, Postnov YV (1987) Genetic analysis of inheritance of rates of Na,K-cotransport calcium concentration in erythrocytes and blood pressure of F2 hybrids of spontaneously hypertensive and normotensive rats. Bull Exp Biol Med 103:518–520

    Article  Google Scholar 

  • Kummerow D, Hamann J, Browning JA, Wilkins R, Ellory JC, Bernhardt I (2000) Variations of intracellular pH in human erythrocytes via K+(Na+)/H+ exchange under low ionic strength conditions. J Membrane Biol 176:207–216

    Article  Google Scholar 

  • Kuro-o M, Hanaoka K, Hiroi Y, Noguchi T, Fujimori Y, Takewaki S, Hayasaka M, Katoh H, Miyagishi A, Nagai R (1995) Salt-sensitive hypertension in transgenic mice over-expressing Na+- proton exchanger. Circ Res 76:148–153

    Article  Google Scholar 

  • Lewiier FI, Canessa M (1985) Red cell transport studies in adult twins. Am J Hum Genet 36:172S

    Google Scholar 

  • Liusov VA, Postnov II, Orlov SN, Riazhskii GG (1983) Differences in the rates of Na/Li-countertransport in the erythrocyte membranes of hypertensive and renal hypertensive patients. Kardiologiia 23:24–26

    Google Scholar 

  • McCormick CP, Hennessy JF, Rauch AL, Buckalew VM Jr (1989) Erythrocyte sodium concentration and 86Rb uptake in weanling Dahl rats. Am J Hypertens 2:604–609

    Article  Google Scholar 

  • Montenay-Garestier T, Aragon I, Devynck MA, Meyer P, Helene C (1981) Evidence for structural changes in erythrocyte membranes of spontaneously hypertension rats. A fluorescence polarization study. Biochem Biophys Res Commun 100:660–665

    Article  Google Scholar 

  • Orlov SN, Postnov II (1981) Erythrocyte membrane permeability of sodium in different types of chronic experimental hypertension. Kardiologiia 21:33–36

    Google Scholar 

  • Orlov SN, Postnov YV (1982) Calcium binding and membrane fluidity in essential and renal hypertension. Clin Sci 63:281–284

    Google Scholar 

  • Orlov SN, Gulak PV, Litvinov IS, Postnov Y (1982) Evidence of altered structure of the erythrocyte membrane in spontaneously hypertensive rats. Clin Sci 63:43–45

    Google Scholar 

  • Orlov SN, Pokudin NI, Postnov Y (1987) Na+/H+ exchange in erythrocytes of spontaneously hypertensive rats. J Hypertens 5:S281–S283

    Google Scholar 

  • Orlov SN, Pokudin NI, Kotelevtsev YV, Postnov YV (1988) Characterization of structural and functional organization of erythrocyte membrane in three strains of spontaneously hypertensive rats. Kardiologiia 28:57–63

    Google Scholar 

  • Orlov SN, Postnov IY, Pokudin NI, Kukharenko VY, Postnov YV (1989a) Na+-H+ exchange and other ion-transport systems in erythrocytes of essential hypertensives and spontaneously hypertensive rats: a comparative analysis. J Hypertens 7:781–788

    Article  Google Scholar 

  • Orlov SN, Pokudin NI, Kotelevtsev YV, Gulak PV (1989b) Volume-dependent regulation of ion transport and membrane phosphorylation in human and rat erythrocytes. J Membrane Biol 107:105–107

    Article  Google Scholar 

  • Orlov SN, Petrunyaka VV, Pokudin NI, Kotelevtsev YV, Postnov YV, Kunes J, Zicha J (1991) Cation transport and adenosine triphophatase activity in rat erythrocytes: a comparison of spontaneously hypertensive rats with the normotensive Brown-Norway strain. J Hypertens 9:977–982

    Google Scholar 

  • Orlov SN, Resink TJ, Bernhardt J, Bühler FR (1992) Volume-dependent regulation of sodium and potassium fluxes in cultured vascular smooth muscle cells: dependence on medium osmolality and regulation by signalling systems. J Membrane Biol 129:199–210

    Article  Google Scholar 

  • Orlov SN, Kolosova IA, Cragoe EJ, Gurlo TG, Mongin AA, Aksentsev SL, Konev SV (1993) Kinetics and peculiarities of thermal inactivation of volume-induced Na/H exchange, Na,K,2Cl cotransport and K,C1 cotransport in rat erythrocytes. Biochim Bio-phys Acta 1151:186–192

    Article  Google Scholar 

  • Orlov SN, Kuznetsov SR, Pokudin NI, Tremblay J, Harnet P (1998) Can we use erythrocytes for the study of the activity of the ubiquitous Na7H+ exchanger (NHE-1) in essential hypertension? Am J Hypertens 11:774–783

    Article  Google Scholar 

  • Orlov SN, Adragna NC, Adarichev VA, Hamet P (1999a) Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension. Am J Physiol 276:C511–C536

    Google Scholar 

  • Orlov SN, Pausova Z, Gossard F, Gaudet D, Tremblay J, Kotchen T, Larochelle P, Hamet P (1999b) Sibling resemblance of erythrocyte ion transporters in French-Canadian sib-pairs affected with essential hypertension. J Hypertens 17:1859–1865

    Article  Google Scholar 

  • Orlov SN, Adarichev VA, Devlin AM, Maximova NV, Sun YL, Tremblay J, Dominiczak AF, Postnov YV, Hamet P (2000) Increased Na7H+ exchanger isoform 1 activity in spontaneously hypertensive rats: lack of mutations within the coding region of NHE1. Biochem Biophys Acta 1500:169–180

    Article  Google Scholar 

  • Orlov SN, Dutil J, Hamet P, Deng AY (2001a) Replacement of a 1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity. Physiol Genomics 7:171–177

    Google Scholar 

  • Orlov SN, Pausova Z, Gossard F, Gaudet D, Tremblay J, Grim CE, Kotchen JM, Kotchen TA, Cowley AW, Larochelle P, Hamet P (2001b) Na+,K+,Cl- cotransport is decreased in African American vs. French-Canadian hypertensives: lack of impact of gender and plasma lipids. J Hypertens 19, suppl 2:S46

    Google Scholar 

  • Page IH (1967) The mosaic theory of arterial hypertension — its interpretation. Perspect Biol Med 10:325–333

    Google Scholar 

  • Pontremoli R, Spalvins A, Menachery A, Torrelli L, Canessa M (1992) Red cell sodium-proton exchange is increased in Dahl salt-sensitive hypertnsive rats. Kidney Int 42:1355–1362

    Article  Google Scholar 

  • Postnov YV, Orlov SN (1984) Cell membrane alteration as a source of primary hypertension. J Hypertens 2:1–6

    Article  Google Scholar 

  • Postnov YV, Orlov SN (1985) Ion transport across plasma membrane in primary hypertension. Physiol Rev 65:904–945

    Google Scholar 

  • Postnov YV, Orlov SN, Shevchenko AS (1975) Alteration of membrane permeability of erythrocytes in rats with spontaneous hypertension. Kardiologiia 15:88–92

    Google Scholar 

  • Postnov YV, Orlov SN, Gulak PV, Shevchenko AS (1976) Altered permeability of the erythrocyte membrane for sodium and potassium in spontaneously hypertensive rats. Pflügers Arch 365:257–263

    Article  Google Scholar 

  • Postnov YV, Orlov SN, Shevchenko AS, Adler AM (1977) Altered sodium permeability, calcium binding and Na-K-ATPase activity in red blood cell membrane in essential hypertension. Pflügers Arch 371:263–270

    Article  Google Scholar 

  • Postnov YV, Kravtsov GM, Orlov SN, Pokudin NJ, Postnov IY, Kotelevtsev YV (1988) Effect of protein kinase C activation on cytoskeleton and cation transport in human erythrocytes. Reproduction of some membrane abnormalities revealed in essential hypertension. Hypertension 12:267–273

    Article  Google Scholar 

  • Rosati C, Meyer P, Garay R (1988) Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats. Hypertension 11:41–48

    Article  Google Scholar 

  • Sen S, Hoffmann GC, Stowe NI, Smeby RR, Bumpus FM (1972) Erythrocytes in spontaneously hypertensive rats. J Clin Invest 51:710–714

    Article  Google Scholar 

  • Shimkets RA, Lifton RP (1996) Recent advances in the molecular genetics of hypertension. Curr Opin Nephrol Hypertens 5:162–165

    Article  Google Scholar 

  • Simon DB, Lifton RP (1996) The molecular basis of inherited hypokalemic alkalosis: Bart-ter’s and Gitelman’s syndromes. Am J Physiol 271:F961–F966

    Google Scholar 

  • Simonet L, St Lezin E, Kurtz TW (1991) Sequence analysis of the alpha 1 Na+,K+-ATPase gene in the Dahl salt- sensitive rat. Hypertension 18:689–693

    Article  Google Scholar 

  • Smith JB, Ash KO, Hunt SC, Hentschel WM, Sprowell W, Dadone MM, Williams RR (1984) Three red cell sodium transport systems in hypertensive and normotensive Utah adults. Hypertension 6:159–166

    Google Scholar 

  • Tripodi G, Valtorta F, Torielli L, Chieregatti E, Salardi S, Trusolino L, Menegon A, Ferrari P, Marchisio PC, Bianchi G (1996) Hypertension-associated point mutations in the ad-ducin a and β subunits affect actin cytoskeleton and ion transport. J Clin Invest 97:2815–2822

    Article  Google Scholar 

  • Tripodi G, Szpirer C, Reina C, Szpirer J, Bianchi G (1997) Polymorphism of gamma-adducin gene in genetic hypertension and mapping of the gene to rat chromosome lq55. Biochem Biophys Res Commun 237:685–689

    Article  Google Scholar 

  • Tuck ML, Gross C, Maxwell MH, Brickman AS, Krasnoshtein G, Mayes D (1984) Erythrocyte Na+,K+ cotransport and Na+,K+ pump in black and Caucasian hypertensive patients. Hypertension 6:536–544

    Article  Google Scholar 

  • Tuck ML, Corry DB, Maxwell M, Stern N (1987) Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension. Hypertension 10:204–211

    Article  Google Scholar 

  • Woods JW, Falk RJ, Pittman AW, Klemmer PJ, Watson BS, Namboodiri K (1982) Increased red-cell sodium-lithium countertransport in normotensive sons of hypertensive parents. N Engl J Med 306:593–595

    Article  Google Scholar 

  • Zicha J (1993) Red cell ion transport abnormalities in experimental hypertension. Fundam Clin Pharmacol 7:129–141

    Article  Google Scholar 

  • Zicha J, Duhm J (1990) Kinetics of Na+ and K+ transport in red blood cells of Dahl rats. Effects of age and salt. Hypertension 15:612–627

    Article  Google Scholar 

  • Zicha J, Kunes J, Devynck MA (1999) Abnormalities of membrane function and lipid metabolism in hypertension: a review. Am J Hypertens 12:315–331

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Pathophysiology of Ion Transport Disorders, Research Centre, University of Montreal Hospital, CHUM, 3850 rue St.-Urbain, Montreal, PQ, H2W 1T8, Canada

    Sergei N. Orlov

  2. Laboratory of Physico-Chemistry of Biomembranes, Faculty of Biology, Lomonosov Moscow State University, Moscow, 119899, Russia

    Sergei N. Orlov

Authors
  1. Sergei N. Orlov
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Naturwissenschaftlich-Technische Fakultät III, Arbeitsgruppe Biophysik, Universität des Saarlandes, P.O.Box 151150, 66041, Saarbrücken, Germany

    Ingolf Bernhardt

  2. Laboratory of Physiology, University of Oxford, Parks Road, Oxford, OX1 3PT, UK

    J. Clive Ellory

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Orlov, S.N. (2003). Hypertension. In: Bernhardt, I., Ellory, J.C. (eds) Red Cell Membrane Transport in Health and Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05181-8_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-05181-8_25

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-07920-7

  • Online ISBN: 978-3-662-05181-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation