Many Membrane Abnormalities in Hypertension Result from one Primary Defect

  • David F. Bohr
  • Philip B. Furspan
  • Anna F. Dominiczak
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 304)


Ever since experimental tools have been available to study cellular mechanisms responsible for hypertension, special attention has been given to the possible role of an abnormality of the cell membrane in this process. This focus evolved not only because all regulatory processes of the cell must be mediated through a cell membrane function, but also because specific clues suggested that the cell membrane might be at fault. Both experimental and clinical hypertension were shown to be influenced by salt intake, implying that some subjects had a defect in regulating salt metabolism, perhaps a problem of cell membrane permeability to sodium or chloride. This idea was supported by the observation that mineralocorticoid excess, which was known to alter membrane permeability to sodium, caused hypertension.


Vascular Smooth Muscle Essential Hypertension Sarcoplasmic Reticulum Normotensive Control Tail Artery 
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  1. Adeoya, A. S., Norman, R. L, and Bing, R. F., 1989, Erythrocyte membrane calcium adenosine 5′-triphosphatase activity in the spontaneously hypertensive rat, Clin. Sci., 77: 395.PubMedGoogle Scholar
  2. Allen, J. C. and Seidel, C., 1977, EGTA stimulated and ouabain inhibited ATPase of vascular smooth muscle, in: “Excitation-Contraction Coupling in Smooth Muscle”, R. Casteels, T. Goodfraind, and J. C. Rüegg, eds., Elsevier/North Holland, Amsterdam, p. 211.Google Scholar
  3. Aoki, K. and Asano, M., 1986, Effect of BAY K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats, Br. J. Pharmacol., 88: 221.PubMedGoogle Scholar
  4. Aaronson, P. S., 1983, Red cell sodium-lithium countertransport and essential hypertension, N. Eng. J. Med., 307: 317.Google Scholar
  5. Berk, B. C., Vallega, G., Muslin, A. J., Gordon, H. M., Canessa, M., and Alexander, R. W., 1989, Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+-H+ exchange, J. Clin. Invest., 83: 822.PubMedCrossRefGoogle Scholar
  6. Berridge, M. J. and Irvine, R. F., 1984, Inositol triphosphate, a novel second messenger in cellular signal transduction, Nature, 312: 315.PubMedCrossRefGoogle Scholar
  7. Besterman, J. M., Duronio, V., and Cuatrecasas, P., 1986, Rapid formation of diacylglycerol from phosphatidylcholine: A pathway for generation of a second messenger, Proc. Nat’l. Acad. Sci. U.S.A., 83: 6785.CrossRefGoogle Scholar
  8. Bialecki, R. A. and Tulenko, T. N., 1989, Excess membrane cholesterol alters calcium channels in arterial smooth muscle, Am. J. Physiol., 257: C306.PubMedGoogle Scholar
  9. Bing, R. F., Heagerty, A. M., Thurston, H., and Swales, J. D., 1986, Ion transport in hypertension: Are changes in the cell membrane responsible?, Clin. Sci., 71: 225.PubMedGoogle Scholar
  10. Broderick, R., Bialecki, R., and Tulenko, T. N., 1989, Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation, Am. J. Physiol, 257: H170.PubMedGoogle Scholar
  11. Bruner, C. A., Webb, R. C., and Bohr, D. F., 1989, Vascular reactivity and membrane stabilizing effect of calcium in spontaneously hypertensive rats, in: “Calcium in Essential Hypertension”, K. Aoki and E. D. Frolich, eds., Academic Press, Tokyo, p. 275.Google Scholar
  12. Bruschi, G., Bruschi, M. E., Cavatorta, A., and Borghetti, A., 1986, The mechanism of Ca increase in blood cells of spontaneously hypertensive rats. J. Cardiovasc. Pharmacol., 8(Suppl 8): S139.PubMedCrossRefGoogle Scholar
  13. Cabot, M. C., Welsh, C. J., Cao, H., and Chabbott, H., 1988, The phosphatidylcholine pathway of diacylglycerol formation stimulated by phorbol diester occurs via phospholipase D activation, FEBS Lett., 233: 153.PubMedCrossRefGoogle Scholar
  14. Canessa, M., Adragna, N., Solomon, H. S., Connolly, T., and Tosteson, D. C., 1980, Increased sodium-lithium countertransport in red cells of patients with essential hypertension, N. Eng. J. Med., 302: 772.CrossRefGoogle Scholar
  15. Carruthers, A. and Melchior, D. L., 1986, How bilayer lipids affect membrane protein activity, Trends Biochem. Sci., 11: 331.CrossRefGoogle Scholar
  16. Criado, M., Eibl, H., and Barrantes, F. J., 1982, Effects of lipid on acetylcholine receptor: Essential need for cholesterol for maintenance of agonist-induced state transition in lipid vesicles, Biochemistry, 21: 362.Google Scholar
  17. Devynck, M. A., Pernollet, M. G., Nunez, A. M., and Meyer, P., 1981, Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rat, Hypertension, 3: 397.PubMedGoogle Scholar
  18. Devynck, M. A., Pernollet, M. G., Nunez, A, M., Aragon, I., Montenay-Garestier, T., Helene, C., and Meyer, P., 1982, Diffuse structural alteration in cell membranes of spontaneously hypertensive rats, Proc. Nat’l. Acad. Sci. U.S.A., 79: 5057.CrossRefGoogle Scholar
  19. Furspan, P. B. and Bohr, D. F., 1985, Lymphocyte abnormalities in three types of hypertension in the rat, Hypertension, 7: 860.PubMedGoogle Scholar
  20. Furspan, P. B. and Bohr, D. F., 1986, Calcium related abnormalities in lymphocytes from genetically hypertensive rats, Hypertension, 8(Suppl II): 11–123.Google Scholar
  21. Furspan, P. B. and Bohr, D. F., 1988, Cell membrane permeability in hypertension, Clin. Physiol. Biochem., 6: 122.PubMedGoogle Scholar
  22. Hagen, E. C., Johnson, J. C., and Webb, R. C., 1982, Ouabain binding and potassium relaxation in aortae from renal hypertensive rabbits, Am. J. Physiol, 12:H896.Google Scholar
  23. Hamet, P. and Tremblay, J., 1989, Abnormalities of second messenger systems in hypertension, in: “Blood cells and arteries in hypertension and atherosclerosis”, P. Meyer and P. Marche, eds., Raven Press, New York, p. 171.Google Scholar
  24. Hansen, T. R. and Bohr, D. F., 1975, Hypertension, transmural pressure, and vascular smooth muscle response in rats, Circ. Res., 36: 590.PubMedGoogle Scholar
  25. Heagerty, A. M., Ollerenshaw, J. D., and Swales, J. D., 1986a, Abnormal vascular phosphoinositide hydrolysis in the spontaneously hypertensive rat, Br. J. Pharmacol., 89: 803.PubMedGoogle Scholar
  26. Heagerty, A. M., Ollerenshaw, J. D., Robertson, D. I., Bing, R. F., and Swales, J. D., 1986b, Influence of dietary linoleic acid on leucocyte sodium transport and blood pressure, Br. Med. J., 293: 295.CrossRefGoogle Scholar
  27. Hoffman, P., Taube, C., and Heinroth-Hoffman, I., 1985, Antihypertensive action of dietary polyunsaturated fatty acids in spontaneously hypertensive rats, Arch. Int. Pharmacodyn. Ther., 276: 222.Google Scholar
  28. Holloway, E. T. and Bohr, D.F., 1973, Reactivity of vascular smooth muscle in hypertensive rats, Circ. Res., 33: 678.PubMedGoogle Scholar
  29. Jones, A. W., 1973, Altered ion transport in vascular smooth muscle from spontaneously hypertensive rats. Influences of aldosterone, norepinephrine, and angiotensin, Circ. Res., 33: 563.PubMedGoogle Scholar
  30. Jones, A. W. and Hart, R. G., 1975, Altered ion transport in aortic smooth muscle during deoxycorticosterone acetate hypertension in the rat, Circ. Res., 37: 333.PubMedGoogle Scholar
  31. Joshua, I. G. and Bohr, D. F., Increased vascular reactivity to endothelin in genetically hypertensive rats, Hypertension, submitted.Google Scholar
  32. Kato, H. and Takenawa, T., 1987, Phospholipase C activation and diacyl-glycerol kinase inactivation lead to an increase in diacylglycerol content in spontaneously hypertensive rat, Biochem. Biophys. Res. Commun., 146: 1419.PubMedCrossRefGoogle Scholar
  33. Kawahara, J., Sano, H., Yoshihisa, K., Hattori, K., Miki, T., Suzuki, H., and Fukuzaki, H., 1990, Dietary linoleic acid prevents the development of deoxycorticosterone acetate-salt hypertension, Hypertension, 15(Suppl I): 1–81.Google Scholar
  34. Koutouzov, S., Marche, P., Girad, A., and Meyer, P., 1983, Altered turnover of polyphosphoinositides in the erythrocyte membrane of the spontaneously hypertensive rat, Hypertension, 5: 409.PubMedGoogle Scholar
  35. Koutouzov, S., Remmal, A., Marche, P., and Meyer, P., 1987, Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats, Hypertension, 10: 497.PubMedGoogle Scholar
  36. Kowarski, S., Cowen, L. A., and Schachter, D., 1986, Decreased content of integral membrane calcium-binding protein (IMCAL) in tissues of the spontaneously hypertensive rat, Proc. Nat’l. Acad. Sci. U.S.A., 83: 1097.CrossRefGoogle Scholar
  37. Kwan, C. Y., Belbeck, L., and Daniel, E. E., 1979, Abnormal biochemistry of vascular smooth muscle plasma membrane as an important factor in the initiation and maintenance of hypertension in rats, Blood Vessels, 16: 259.PubMedGoogle Scholar
  38. Lamb, F. S., Myers, J. H., Hamlin, M. N., and Webb, R. C., 1985, Oscillatory contractions in tail arteries from genetically hypertensive rats, Hypertension, 7(Suppl. I): 1–25.Google Scholar
  39. Livne, A., Veitch, R., Grinstein, S., Balfe, J. W., Marquez-Julio, A., and Rothstein, A., 1987, Increased platelet Na+-H+ exchange rates in essential hypertension: Application of a novel test, Lancet, 1: 553.Google Scholar
  40. Locher, R., Neyses, M., Stimpel, M., Kuffer, B., and Vetter, W., 1984, The cholesterol content of the human erythrocyte influences calcium influx through the channel, Biochem. Biophys. Res. Commun., 124: 822.PubMedCrossRefGoogle Scholar
  41. MacDonald, M. C., Kline, R. L., and Mogenson, G. J., 1980, Dietary linoleic acid and salt-induced hypertension, Can. J. Physiol. Pharmacol., 59: 872.CrossRefGoogle Scholar
  42. Madden, T. D., Chapman, D., and Quinn, P. J., 1979, Cholesterol modulates activity of calcium-dependent ATPase of the sarcoplasmic reticulum, Nature, 279: 538.PubMedCrossRefGoogle Scholar
  43. Marche, P., Limon, I., Blanc, J., and Girard, A., 1990, Platelet phosphatidylcholine turnover in experimental hypertension, Hypertension, 16: 190.PubMedGoogle Scholar
  44. Moreland, R. S., Lamb, F. S., Webb, R. C., and Bohr, D. F., 1984, Functional evidence for increased sodium permeability in aortas from DOCA hypertensive rats, Hypertension, 6(Suppl I): 1–88.Google Scholar
  45. Murray, G. E., Nair, R., and Patrick, J., 1986, The effect of dietary polyunsaturated fat on cation transport and hypertension in the rat, Br. J. Nutrition, 56: 587.CrossRefGoogle Scholar
  46. Naftilan, A. J., Dzau, V. J., and Loscalzo, J., 1986, Preliminary observations on abnormalities of membrane structure and function in essential hypertension, Hypertension, 8(Suppl II): II–174.Google Scholar
  47. Nara, Y., Sato, T., Mochizuki, S., Mano, M., Horie, R., and Yamori, Y., 1986, Metabolic dysfunction in smooth muscle cells of spontaneously hypertensive rats, J. Hypertension, 4(Suppl III): S105.Google Scholar
  48. Neer, E. J. and Clapham, D. E., 1988, Role of G protein subunits in transmembrane signalling, Nature, 333: 129.PubMedCrossRefGoogle Scholar
  49. Noon, J. P., Rice, P. I., and Baldassani, R. J., 1978, Calcium leakage as a cause of high resting tension in vascular smooth muscle from spontaneously hypertensive rat, Proc. Nat’l., Acad. Sci. U.S.A., 75: 1605.CrossRefGoogle Scholar
  50. Okumura, K., Kondo, J., Shirai, Y., Muramatsu, M., Yamada, Y., Hashimoto, H., and Ito, T.. 1990, 1,2-diacylglycerol content in thoracic aorta of spontaneously hypertensive rats, Hypertension, 16: 43.PubMedGoogle Scholar
  51. Ollerenshaw, J. D., Heagerty, A. M., Bing, R. F., and Swales, J. D., 1987, Abnormalities of erythrocyte membrane fatty acid composition in human essential hypertension, J. Human Hypertension, 1: 9.Google Scholar
  52. Orlov, S. N. and Postnov, Y. V., 1982, Ca2+ binding and membrane fluidity in essential and renal hypertension, Clin. Sci., 63: 281.PubMedGoogle Scholar
  53. Orlov, S. N., Gulak, P. V., Litvinov, I. S., and Postnov, Y. V., 1982, Evidence of altered structure of the erythrocyte membrane in spontaneously hypertensive rats, Clin. Sci., 63: 43.PubMedGoogle Scholar
  54. Postnov, Y. V., Orlov, S. N., and Pokudin, N. J., 1980, Decrease of calcium binding by red blood cell membrane in spontaneously hypertensive rats and in essential hypertension, Pflügers Arch., 385: 191.CrossRefGoogle Scholar
  55. Rao, R. H., Rao, V. B., and Stikantia, S. G., 1981, Effect of polyunsaturated-rich vegetable oils on blood pressure in essential hypertension, Clin. Exp. Hypertension, 3: 27.CrossRefGoogle Scholar
  56. Rasmussen, H., Tukuwa, Y., and Park, S., 1987, Protein kinase C in the regulation of smooth muscle contraction, FASEB J., 1: 177.PubMedGoogle Scholar
  57. Remmal, A., Koutouzov, S., and Marche, P., 1988, Enhanced turnover of phosphatidylcholine in platelets of hypertensive rats. Possible involvement of a phosphatidylcholine-specific phospholipase C., Biochim. Biophys. Acta, 690: 236.Google Scholar
  58. Rothstein, A., 1968, Membrane phenomena, Ann. Rev. Physiol, 30: 15.CrossRefGoogle Scholar
  59. Rush, N. J. and Hermsmeyer, K., 1988, Calcium currents are altered in the vascular muscle cell membrane of spontaneously hypertensive rats, Circ. Res., 63: 997.Google Scholar
  60. Shlatz, L. and Marinetti, G. V., 1972, Calcium binding to the rat liver plasma membrane, Biochim. Biophys. Acta, 290: 70.PubMedCrossRefGoogle Scholar
  61. Siegel, D. P., Banschbach, J., Alford, D., Ellens, H., Lis, L. J., Quinn, P. J., Yeagle, P. L., and Bentz, J., 1989, Physiological levels of diacylglycerols in phospholipid membranes induce membrane fusion and stabilize inverted phases, Biochemistry, 28: 3703.PubMedCrossRefGoogle Scholar
  62. Singer, S. J. and Nicolson, G. L., 1972, The fluid mosaic model of the structure of cell membranes, Science, 175: 720.PubMedCrossRefGoogle Scholar
  63. Soltis, E. E. and Bohr, D. F., 1987, Vascular reactivity in the spontaneously hypertensive stroke-prone rat: Effect of antihypertensive treatment, Hypertension, 9: 492.PubMedGoogle Scholar
  64. Storm, D. S., Turla, M. B., Todd, K. M., and Webb, R. C., 1990, Calcium and contractile responses to phorbol esters and the calcium channel agonist, Bay K 8644, in arteries from hypertensive rats, Am. J. Hypertension, 3: 245S.Google Scholar
  65. Suzuki, A., Yanagawa, T., and Tajiri, T., 1979, Effects of some smooth muscle relaxants on the tonus and on the actions of contractile agents in isolated aorta of SHRSP, Jpn. Heart J., 20(Suppl 1): 219.Google Scholar
  66. Swanson, J. E., Lokesh, B. R., and Kinsella, J. E., 1989, Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content, J. Nutrition, 119: 364.Google Scholar
  67. Takaya, J., Lasker, N., Bamforth, R., Gutkin, M., Byrd, L. H., and Aviv, A., 1990, Kinetics of Ca2+-ATPase activation in platelet membranes of essential hypertensives and normotensives, Am. J. Physiol, 258: C988.PubMedGoogle Scholar
  68. Thompson, L. E., Rinaldi, G. J., and Bohr, D. F., 1990, Decreased activity of the sodium-calcium exchanger in tail artery of stroke-prone spontaneously hypertensive rats, Blood Vessels, 27: 197.PubMedGoogle Scholar
  69. Turla, M. B. and Webb, R. C., 1987, Enhanced vascular reactivity to protein kinase C activators in genetically hypertensive rats, Hypertension, 9(Suppl III): III–150.Google Scholar
  70. Turla, M. B. and Webb, R. C., 1990, Augmented phosphoinositide metabolism in aortas from genetically hypertensive rats, Am. J. Physiol., 258: H173.PubMedGoogle Scholar
  71. Van Breemen, C., Leijten, P., Yamamoto, H., Aaronson, P., and Cauvin, C., 1986, Calcium activation of vascular smooth muscle, Hypertension, 8(Suppl II): II–89.Google Scholar
  72. Van Breemen, C. and Saida, K., 1989, Cellular mechanisms regulating [Ca2+]i in smooth muscle, Ann. Rev. Physiol, 51: 315.CrossRefGoogle Scholar
  73. Wähle, K. W. J., 1983, Fatty acid modification and membrane lipids, Proc. Nutrition Soc., 42: 273.CrossRefGoogle Scholar
  74. Webb, R. C., 1982, Potassium relaxation of vascular smooth muscle from DOCA hypertensive pigs, Hypertension, 4: 609.PubMedGoogle Scholar
  75. Webb, R. C. and Bohr, D. F., 1984, The membrane of the vascular smooth muscle cell in experimental hypertension and its response to serotonin. in: “Smooth Muscle Contraction”, N. L. Stephens, ed., M. Dekker, Inc., New York, p. 485.Google Scholar
  76. Webb, R. C. and Bohr, D. F., 1978, Mechanism of membrane stabilization by calcium in vascular smooth muscle, Am. J. Physiol., 235: C227.PubMedGoogle Scholar
  77. Webb, R. C. and Bohr, D. F., 1979, Potassium relaxation of vascular smooth muscle from spontaneously hypertensive rats, Blood Vessels, 16: 71.PubMedGoogle Scholar
  78. Weiss, G. B., 1986, Phospholipids, calcium binding and arterial smooth muscle membranes, in: “Recent Advances in Arterial Diseases: Atherosclerosis, Hypertension and Vasospasm”, T. N. Tulenko and R. H. Cox, eds., Alan R. Liss, New York, p. 123.Google Scholar
  79. Yeagle, P. L., 1983, Cholesterol modulation of (Na+ + K+) ATPase ATP hydrolyzing activity in human erythrocyte, Biochim. Biophys. Acta, 727: 39.PubMedCrossRefGoogle Scholar
  80. Yeagle, P. L., 1989, Lipid regulation of cell membrane structure and function, FASEB J., 3: 1833.PubMedGoogle Scholar
  81. Yeagle, P. L. and Sen, A., 1986, Hydration and the lamellar to hexagonal II phase transition of phosphatidylethanolamine, Biochemistry, 25: 7518.PubMedCrossRefGoogle Scholar
  82. Yeagle, P. L., Young, J., and Rice, D., 1988, Effects of cholesterol on (Na+, K+) ATPase ATP hydrolyzing activity in bovine kidney, Biochemistry, 27: 6449.PubMedCrossRefGoogle Scholar
  83. Zolese, G. and Curatola, G., 1989, Ca2+ interaction with phospholipid bilayers studied by multifrequency phase fluorometry, Biosci. Rep., 9: 497.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • David F. Bohr
    • 1
  • Philip B. Furspan
    • 1
  • Anna F. Dominiczak
    • 1
  1. 1.Department of PhysiologyUniversity of Michigan School of MedicineAnn ArborUSA

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