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The role of renin in the control of the circulation and in hypertensive disease

  • Edgar Haber
Nuclear Medicine Section Editorials
  • 11 Downloads

Summary

Renin is a hormone secreted by the juxtaglomerular cells of the kidney; it interacts with a plasma protein substrate to produce a decapeptide prohormone angiotensin I. Converting hormone located on vascular endothelium converts the decapeptide to an octapeptide, angiotensin II, which effects vasoconstriction, the secretion of aldosterone by the adrenal cortex, and retention of sodium by the kidney. The biosynthesis and control of renin secretion are not well understood, and the question as to whether renin is synthesized and stored in a larger precursor form is as yet unresolved. Whether or not higher molecular weight or inactive forms of renin in plasma have a role in controlling renin activity or whether they simply represent a degradative pathway for renin is as yet uncertain. The availability of several inhibitors of the renin-angiotensin system has served to define the role of renin both in normal cardiovascular homeostasis and in renovascular hypertension. It appears that renin plays an important role in maintaining blood pressure in the salt- or volume-depleted state and that it is responsible for the initial phases of renovascular hypertension in any model of this disease process. Renin's part in chronic renovascular hypertension depends on whether or not sodium is permitted to accumulate. If sodium intake is restricted or if sodium excretion is unimpaired (such as in two-kidney renovascular hypertension models), renin continues to play a significant role during the chronic phase.

Key-words

Angiotensin Blood pressure Circulation Hypertension Renin 

References

  1. 1.
    Amsterdam E. A., Couch N. P., Christleib A. R., Harrison J. H., Crane C., Dobrizinsky S. J., Hickler R. B.: Renal vein renin activity in the prognosis of surgery for renovascular hypertension—Amer. J. Med.47, 860, 1969.PubMedCrossRefGoogle Scholar
  2. 2.
    Aoyagi T., Kunimoto S., Morishima H., Takeuchi T., Umezawa H.: Effect of pepstatin on acid proteases—J. Antibiot. (Tokyo)24, 687, 1971.Google Scholar
  3. 3.
    Atlas S. A., Sealey J. E., Laragh J. H.: Protease as endogenous activator of inactive renin— Lanceti, 555, 1978.CrossRefGoogle Scholar
  4. 4.
    Bakhle Y. S.: Inhibition of angiotensin I converting enzyme by venom peptides—Brit. J. Pharmacol.43, 252, 1971.Google Scholar
  5. 5.
    Bianchi A., Evans D. B., Cobb M., Peschka M. T., Schaeffer T. R., Laffan R. J.: Inhibition by SQ20881 of vasopressor response to angiotensin I in conscious animals—Europ. J. Pharmacol.23, 90, 1973.CrossRefGoogle Scholar
  6. 6.
    Bing J., Nielson K.: Role of the renin-system in normo- and hypertension. Effect of angiotensin inhibitor (1-Sar-8-Ala-angiotensin II) on the blood pressure of conscious or anesthetized normal, nephrectomized, and renal hypertensive rats—Acta path. microbiol. scand. (A)81, 254, 1973.Google Scholar
  7. 7.
    Blair-West J. R., Coghlan J. P., Denton D. A., Funder J. W., Scoggins B. A., Wright R. D.: The effects of the heptapeptide (2–8) and hexapeptide (3–8) fragments of angiotensin II on aldosterone secretion—J. clin. Endocr.32, 575, 1971.PubMedGoogle Scholar
  8. 8.
    Blair-West J. R., Coghlan J. P., Denton D. A., Funder J. W., Scoggins B. A., Wright R. D.: Inhibition of renin secretion by systemic and intrarenal angiotensin infusion—Amer. J. Physiol.220, 1309, 1971.PubMedGoogle Scholar
  9. 9.
    Boucher R., Demassieux S., Garcia R., Genest J.: Tonin-angiotensin II system. A review —Circulat. Res.41 (Suppl. 2), 26, 1977.PubMedGoogle Scholar
  10. 10.
    Boucher R., Garcia R., Demassieux S., Gutkowska J., Genest J.: Tonin-angiotensin system in hypertension—In: Proceedings of the 5th Meeting of the International Society of Hypertension, 1978—Clin. Sci. mol. Med.55 (Suppl. 4), 183s, 1978.Google Scholar
  11. 11.
    Boyd G. W.: A protein-bound form of porcine renal renin—Circulat. Res.35, 426, 1974.PubMedGoogle Scholar
  12. 12.
    Brunner H. R., Gavras H., Laragh J. H., Keenan R.: Angiotensin II blockade in man by Sar1-Ala8-angiotensin II for understanding and treatment of high-blood pressure—Lancetii, 1045, 1973.CrossRefGoogle Scholar
  13. 13.
    Brunner H. R., Kirshman J. D., Sealey J. E., Laragh J. H.: Hypertension of renal origin: evidence for two different mechanisms—Science174, 1344, 1971.PubMedCrossRefGoogle Scholar
  14. 14.
    Bumpus F. M., Sen S., Smeby R. R., Sweet C. S., Ferrario C. M., Khosla M. C.: Use of angiotensin II antagonists in experimental hypertension—Circulat. Res.32 (Suppl. 1), 150, 1973.PubMedGoogle Scholar
  15. 15.
    Bunag R. D., Page I. H., McCubbin J. W.: Inhibition of renin release by vasopressin and angiotensin—Cardiovasc. Res.1, 67, 1967.PubMedCrossRefGoogle Scholar
  16. 16.
    Burton J., Poulsen K., Haber E.: Competitive inhibitors of renin: inhibitors effective at physiological pH—Biochemistry14, 3892, 1975.PubMedCrossRefGoogle Scholar
  17. 17.
    Day R. P., Leutscher J. A.: Biochemical properties of big renin extracted from human plasma—J. clin. Endocr.40, 1085, 1975.PubMedGoogle Scholar
  18. 18.
    Day R. P., Leutscher J. A., Gonzales C. M.: Occurrence of big renin extracted from human plasma, amniotic fluid and kidney extracts—J. clin. Endocr.40, 1078, 1975.PubMedGoogle Scholar
  19. 19.
    Day R. P., Leutscher J. A., Zager P. G.: Big renin; identification, chemical properties and clinical implications—Amer. J. Cardiol.37, 667, 1976.PubMedCrossRefGoogle Scholar
  20. 20.
    DeChamplin J., Genest J., Veyratt R., Boucher R.: Factors controlling renin in man —Arch. intern. Med.117, 355, 1966.Google Scholar
  21. 21.
    Deodhar S. D., Haas E., Goldblatt H.: Production of antirenin to homologous renin and its effect on experimental renal hypertension—J. exp. Med.119, 425, 1964.PubMedCrossRefGoogle Scholar
  22. 22.
    Derkx F. H. M., van Gool J. M. G., Wenting G., Verhoeven R. P., Man in't Veld A. J., Schalekemp M. A. D. H.: Inactive renin in human plasma—Lancetii, 496, 1976.CrossRefGoogle Scholar
  23. 23.
    Donker A. J. M., Leenen F. H. H.:: Infusion of angiotensin II-analogue in two patients with unilateral renovascular hypertension—Lancetii, 1535, 1974.CrossRefGoogle Scholar
  24. 24.
    Edelman R., Hartroft P. M.: Localization of renin in juxtaglomerular cells of rabbit and dog through the use of the fluorescent-antibody technique—Circulat. Res.9, 1060, 1961.Google Scholar
  25. 25.
    Ferreira S. H.: A bradykinin-potentiating factor (BPF) present in the venom ofBothrops jararaca—Brit. J. Pharmacol.24, 163, 1965.PubMedGoogle Scholar
  26. 26.
    Fitz A.: Renal venous determinations in the diagnosis of surgically correctable hypertension— Circulation36, 942, 1967.PubMedGoogle Scholar
  27. 27.
    Franze de Fernandez M. T., Paladini A. C., Deluis A. E.: Isolation and characterization of a pepsitensin—Biochem. J.97, 540, 1965.Google Scholar
  28. 28.
    Freedman R. H., Davis J. O., Lohmeier T. E.: Des-1-Asp-angiotensin II: possible intrarenal role in homeostasis in the dog—Circulat. Res.37, 30, 1975.Google Scholar
  29. 29.
    Gavras H., Brunner H. R., Laragh J. H., Sealey J. E., Gavras I., Vukovich R. A.: An angiotensin converting enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients—New Engl. J. Med.291, 817, 1974.PubMedGoogle Scholar
  30. 30.
    Gavras H., Brunner H. R., Turini G. A., Kershaw G. R., Tifft C. P., Cuttelod S., Gavras I., Vukovich R. A., McKinstry D. N.: Antihypertensive effect of the oral angiotensin converting enzyme inhibitor SQ 14225 in man—New Engl. J. Med.298, 991, 1978.PubMedGoogle Scholar
  31. 31.
    Gavras H., Brunner H. R., Vaughan E. D., Jr.,Laragh J. H.: Angiotensin-sodium interaction in blood pressure maintenance of renal hypertensive and normotensive rats—Science180, 1369, 1973.PubMedCrossRefGoogle Scholar
  32. 32.
    Goodfriend T., Allman D., Kent K., Dempsey P., Cooper T.: Angiotensin's inotropic and mitochondrial effects—Clin. Res.19, 316, 1971.Google Scholar
  33. 33.
    Goormaghtigh N.: Existence of an endocrine gland in the media of the renal arterioles— Proc. Soc. exp. Biol. (N.Y.)42, 688, 1939.Google Scholar
  34. 34.
    Gross F., Lazar J., Orth H.: Inhibition of the renin-angiotensinogen reaction by pepstatin— Science175, 656, 1972.PubMedCrossRefGoogle Scholar
  35. 35.
    Guyton A. C., Coleman T. G., Granger H. J.: Circulation: overall regulation—Ann. Rev. Physiol.34, 13, 1972.CrossRefGoogle Scholar
  36. 36.
    Hodge R. L., Ng K. K. F., Vane J. R.: Disappearance of angiotensin from the circulation of the dog—Nature (Lond.)215, 138, 1967.CrossRefGoogle Scholar
  37. 37.
    Inagami T., Murakami K.: Purification of high molecular weight forms of renin from hog kidney—Circulat. Res.41 (Suppl. 2), 16, 1977.Google Scholar
  38. 38.
    Johnson J. A., Davis J. O.: Effects of a specific competitive antagonist of angiotensin II on arterial pressure and adrenal steroid secretion in dogs—Circulat. Res.32 (Suppl. 1), 159, 1973.PubMedGoogle Scholar
  39. 39.
    Johnson J. A., Davis J. O., Spielman W. S., Freeman R. H.: The role of the renin-angiotensin system in experimental renal hypertension in dogs—Proc. Soc. exp. Biol. (N.Y.)147, 387, 1974.Google Scholar
  40. 40.
    Judson W. E., Helmer O. M.: Diagnostic and prognostic values of renin activity in renal venous plasma in renovascular hypertension—Hypertension13, 79, 1965.Google Scholar
  41. 41.
    Khosla M. C., Smeby R. R., Bumpus F. M.: Structure-activity relationships in angiotensin I analogs—In:Page H., Bumpus F. M. (Eds) Angiotensin. Springer-Verlag, Berlin, 1974; p. 126.Google Scholar
  42. 42.
    Kokubu T., Hiwada K., Nagasaka Y., Yamamura Y.: Effect of several proteinase inhibitors on renin reaction—Jap. Circulat. J. (En.)38, 955, 1974.Google Scholar
  43. 43.
    Krieger E. M., Salgado H. C., Assan C. J., Greene L. L. J., Ferreira S. H.: Potential screening test for detection of overactivity of renin-angiotensin system—Lanceti, 269, 1971.CrossRefGoogle Scholar
  44. 44.
    Laragh J. H., Sealey J. E., Buhler F. R., Vaughan E. D., Brunner H. R., Gavras H., Baer L.: The renin axis and vasoconstrictor volume analysis for understanding and treating renovascular and renal hypertension—Amer. J. Med.58, 4, 1975.PubMedCrossRefGoogle Scholar
  45. 45.
    Leckie B. J., McConnell A.: A renin inhibitor from rabbit kidney: conversion of a large inactive renin to a smaller active enzyme—Circulat. Res.36 513, 1975.PubMedGoogle Scholar
  46. 46.
    Leckie B. J., McConnell A.: Acid-activation of renin in human kidney extracts and plasma— Acta endocr. (Kbh.),199 (Suppl.), 280, 1975.Google Scholar
  47. 47.
    Levine M., Lentz K. E., Kahn J. R., Dorer F. E., Skeggs L. T., Jr.: Pattial purification of a high molecular weight renin from hog kidney—Circulat. Res.38, (Suppl. 2), 90, 1976.PubMedGoogle Scholar
  48. 48.
    Lumbers E. R.: Activation of renin in human amniotic fluid by low pH—Enzymologia40, 329, 1971.PubMedGoogle Scholar
  49. 49.
    Malling C., Poulsen K.: A direct radioimmunoassay for plasma renin in mice and its evaluation—Biochim. biophys. Acta (Amst.)491, 532, 1977.Google Scholar
  50. 50.
    Marks L. S., Maxwell M. H.: Renal vein renin: value and limitations in the prediction of operative results—Urol. Clin. North Amer.2, 311, 1975.Google Scholar
  51. 51.
    Marks L. S., Maxwell M. H., Varady P. D.: Renovascular hypertension: does the renal vein ratio predict operative results?—J. Urol. (Baltimore)115 365, 1976.Google Scholar
  52. 52.
    Menard J., Gardes J., Kreft C., Evin G., Castro B., Carvol P.: Soluble pepstatin: a new approach for thein vivo blockade of the renin-angiotensin system—In: Proceedings of the 5th Meeting of the International Society of Hypertension, 1978—Clin. Sci. mol. Med55 (Suppl. 4), 167s, 1978.Google Scholar
  53. 53.
    Michelakis A. M., Foster J. H., Liddle G. W., Rhamy R. K., Kuchel O., Gordon R. D.: Measurement of renin in both renal veins: its use in diagnosis of renovascular hypertension— Arch. intern. Med.120, 444, 1967.PubMedCrossRefGoogle Scholar
  54. 54.
    Miller E. D. Jr.,Samuels A. I., Haber E., Barger A. C.: Inhibition of angiotensin conversion in experimental renovascular hypertension—Science177, 1108, 1972.PubMedCrossRefGoogle Scholar
  55. 55.
    Miller E. D. Jr.,Samuels A. I., Haber E., Barger A. C.: Inhibition of angiotensin conversion and prevention of renovascular hypertension—Amer. J. Physiol.228, 448, 1975.PubMedGoogle Scholar
  56. 56.
    Morris B. J., Johnston C. I.: Isolation of renin granules from rat kidney cortex and evidence for an inactive form of renin (prorenin) in granules and plasma—Endocrinology98, 1466, 1976.PubMedGoogle Scholar
  57. 57.
    Morris B. J., Lumbers E. R.: The activation of renin in human amniotic fluid by proteolytic enzymes—Biochim. biophys. Acta (Amst.)289, 385, 1972.Google Scholar
  58. 58.
    Ondetti M. A., Rubin B., Cushman D. W.: Design of specific inhibitors of angiotensin converting enzyme: new class of orally active antihypertensive agents—Science,196, 441, 1977.PubMedCrossRefGoogle Scholar
  59. 59.
    Ondetti M. A., Williams N. J., Sabo E. F., Pluscec J., Weaver E. R., Kocy O.: Angiotensin converting enzyme inhibitors from the venom ofBothrops jararaca: isolating elucidation of structure and synthesis—Biochemistry10, 4033, 1971.PubMedCrossRefGoogle Scholar
  60. 60.
    Oparil S., Haber E.: The renin-angiotensin system—New Engl. J. Med.291 389, 1974.PubMedGoogle Scholar
  61. 61.
    Pals D. T., Masucci F. D., Denning G. S., Jr.,Sipos F., Fessler D. C.: Role of the pressor action of angiotensin II in experimental hypertension—Circulat. Res.29, 673, 1971.PubMedGoogle Scholar
  62. 62.
    Pals D. T., Masucci F. D., Sipos F., Denning G. S., Jr.: A specific competitive antagonist of the vascular action of angiotensin II—Circulat. Res.29, 664, 1971.PubMedGoogle Scholar
  63. 63.
    Poulsen K., Burton J., Haber E.: Competitive inhibitors of renin—Biochemistry12, 3877, 1973.PubMedCrossRefGoogle Scholar
  64. 64.
    Poulsen K., Burton J., Haber E.: Purification of hog renin by affinity chromatography using the synthetic competitive inhibitor [D-Leu6] octapeptide—Biochim. biophys. Acta (Amst.)400, 258, 1975.Google Scholar
  65. 65.
    Poulsen K., Nielson A. H., Lykkegaard S., Malling C. O., Krøll J., Jensenius J.: Is high-molecular-weight binding of renin to the protease inhibitors and lipoproteins?—In: Proceedings of the 5th Meeting of the International Society of Hypertension, 1978—Clin. Sci. mol. Med.55 (Suppl. 4), 125s, 1978.Google Scholar
  66. 66.
    Poulsen K., Sancho J., Haber E.: A simplified radioimmunoassay for plasma aldosterone employing an antibody of unique specificity—Clin. Immunol. Immunopath.2, 373, 1974.CrossRefGoogle Scholar
  67. 67.
    Re R. N., Novelline R., Escourrou M. T., Athanasoulis C., Burton J., Haber E.: Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis—New Engl. J. Med.298, 582, 1978.PubMedGoogle Scholar
  68. 68.
    Rocchini A. P., Barger A. C.: Renovascular hypertension in sodium-depleted dogs: role of renin in carotid sinus reflex—Amer. J. Physiol. (In press).Google Scholar
  69. 69.
    Romero J. C., Hoobler S. W., Kozak T. J., Warzynski R. J.: Effect of antirenin on blood pressure of rabbits with experimental renal hypertension—Amer. J. Physiol.225, 810, 1973.PubMedGoogle Scholar
  70. 70.
    Rubin E.: Purification of hog renin: properties of purified hog renin—J. clin. Lab. Invest.29, 51, 1972.CrossRefGoogle Scholar
  71. 71.
    Samuels A. I., Miller E. D., Jr.,Fray C. S., Haber E., Barger A. C.: Renin-angiotensin antagonists and the regulation of blood pressure—Fed. Proc.35, 2512, 1976.PubMedGoogle Scholar
  72. 72.
    Sancho J., Re R. N., Burton J., Barger A. C., Haber E.: The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects—Circulation53, 400, 1976.PubMedGoogle Scholar
  73. 73.
    Sancho J., Re R. N., Kliman B., Haber E.: Diurnal variation of plasma aldosterone in low renin hypertension—Circulation50 (Suppl. 3), 202, 1974.Google Scholar
  74. 74.
    Sealey J. E., Laragh J. H.: ‘Prorenin’ in human plasma: methodological and physiological implications—Circulat. Res.36/37 (Suppl. 1), 10, 1975.Google Scholar
  75. 75.
    Sealey J. E., Moon C., Laragh J. H., Atlas S. A.: Plasma prorenin in normal, hypertensive, and anephric subjects and its effect on renin measurements—Circulat. Res.40 (Suppl. 1), 141, 1977.Google Scholar
  76. 76.
    Shade R. E., Davis J. O., Johnson J. A., Gotshall R. W., Spielman W. S.: Mechanism of action of angiotensin II and antidiuretic hormone on renin secretion—Amer. J. Physiol.224, 926, 1973.PubMedGoogle Scholar
  77. 77.
    Skeggs L. T., Jr.Kahn J. R., Lentz K. E., Shumway N. P.: The preparation, purification and amino acid sequence of a polypeptide renin substrate—J. exp. Med.106, 439, 1957.PubMedCrossRefGoogle Scholar
  78. 78.
    Skeggs L. T., Kahn J. R., Levine M., Dorer F. E., Lentz K. E.: Chronic one-kidney hypertension in rabbits. I. Treatment with kidney extracts—Circulat Res.37, 715, 1975.PubMedGoogle Scholar
  79. 79.
    Skeggs L. T., Kahn J. R., Levine M., Dorer F. E., Lentz K. E.: Chronic one-kidney hypertension in rabbits II. Evidence for a new factor—Circulat. Res.39, 400, 1976.PubMedGoogle Scholar
  80. 80.
    Skeggs L. T., Kahn J. R., Levine M., Dorer F. E., Lentz K. E.: Chronic one-kidney hypertension in rabbits. III. Renopressin, a new hypertensive substance—Circulat. Res.40, 143, 1977.PubMedGoogle Scholar
  81. 81.
    Skeggs L. T., Lentz K. E., Kahn J. R., Hochstrasser H.: Studies on the preparation and properties of renin—Circulat. Res.20/21 (Suppl. 2), 91, 1967.Google Scholar
  82. 82.
    Skeggs L. T., Lentz K. E., Kahn J. R., Hochstrasser H.: Kinetics of the reaction of renin with nine synthetic peptide substrates—J. exp. Med.128, 13, 1968.PubMedCrossRefGoogle Scholar
  83. 83.
    Skeggs L. T., Lentz K. E., Kahn J. R., Levine M., Dorer F. E.: Multiple forms of human kidney renin—In:Genest J., Krow E. (Eds): Hypertension. Springer-Verlag, New York, 1972; p. 149.Google Scholar
  84. 84.
    Skinner S. L., Cran E. J., Gibson R., Taylor R., Walters W. A. W., Catt K. J.: Angiotensin I and II, active and inactive renin, renin substrate, renin activity, and angiotensinase in humanliquor amnii and plasma—Amer. J. Obstet. Gynec.121, 626, 1975.PubMedGoogle Scholar
  85. 85.
    Slater E. E., Haber E.: A large form of renin from normal human kidney—J. clin. Endocr.47, 105, 1978.PubMedGoogle Scholar
  86. 86.
    Stockigt J. R., Noakes C. A., Collins R. D.: Renal-vein renin in various forms of renal hypertension—Lanceti, 1194, 1972.CrossRefGoogle Scholar
  87. 87.
    Streeten G. H. P., Anderson G. H., Freiberg J. M., Dalakos T. G.: Use of an angiotensin II antagonist (saralysin) in the recognition of ‘angiotensinogenic’ hypertension—New Engl. J. Med.292, 657, 1975.PubMedGoogle Scholar
  88. 88.
    Tagawa H., Gutmann F. D., Haber E., Miller E. D., Jr.,Samuels A. I., Barger A. C.: Reversible renovascular hypertension and renal arterial pressure—Proc. Soc. exp. Biol. (N. Y.)146, 975, 1974.Google Scholar
  89. 89.
    Tanaka K., Omae T., Hattori N., Katsuki S.: Renin release from ischemic kidneys following angiotensin infusion in dogs—Jap. Circulat. J. (En.)33, 235, 1969.Google Scholar
  90. 90.
    Tobian L., Coffee K., McCrea P.: Contrasting total exchangeable sodium levels in rats with two different types of Goldblatt hypertension—J. Lab. clin. Med.66, 1027, 1965.Google Scholar
  91. 91.
    Vagnucci A. H., McDonald R. H., Jr.,Drash A. L., Wong A. K. C.: Intradian changes of plasma aldosterone, cortisol, corticosterone, and growth hormone in sodium restriction— J. clin. Endocr.38, 761, 1974.PubMedCrossRefGoogle Scholar
  92. 92.
    Vander A. J., Geelhoed G. W.: Inhibition of renin secretion by angiotensin II—Proc. Soc. exp. Biol. (N.Y.)120, 399, 1965.Google Scholar
  93. 93.
    Wakerlin G. E.: Antibodies to renin as proof of the pathogenesis of sustained renal hypertension— Circulation17, 653, 1958.PubMedGoogle Scholar
  94. 94.
    Watkins B. E., Davis J. O., Freeman R. H., DeForrest J. M., Stephens G. A.: Continuous angiotensin II blockade throughout the acute phase of one-kidney hypertension in the dog— Circulat. Res.42, 813, 1978.PubMedGoogle Scholar
  95. 95.
    Winer B. M., Lubbe W. F., Simon M., Williams J. A.: Renin in the diagnosis of renovascular hypertension—J. Amer. med. Ass.202 121, 1967.CrossRefGoogle Scholar
  96. 96.
    Woessner J. F., Jr.: Pepstatin inhibits the digestion of hemoglobin and protein-polysaccharide complex by cathepsin D—Biochem. biophys. Res. Commun.47, 965, 1972.PubMedCrossRefGoogle Scholar
  97. 97.
    Woods J. W., Michelakis A. M.: Renal vein renin in renovascular hypertension—Arch. intern. Med.122, 392, 1968.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • Edgar Haber
    • 1
  1. 1.Cardiac Unit, Department of MedicineMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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