The Renin-Angiotensin System, Converting Enzyme Inhibition, and Antihypertensive Therapy

Part of the Progress in Hormone Biochemistry and Pharmacology book series (PRHO, volume 1)


In the past 80 years, the renin-angiotensin-aldosterone system, the kallikrein-kinin-prostaglandin system, and the role of the angiotensin- converting enzyme have been undergoing ever-increasing investigation in the pathogenesis of hypertension and in related cardiovascular disorders. Much insight has been obtained, but, controversial findings in some areas give further promise of even more biochemical and physiological, and pharmacological studies and analyses in animals and in man.


Plasma Renin Activity Renovascular Hypertension Mean Blood Pressure Aldosterone Secretion Renal Hypertension 
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  1. 1.
    Ondetti, M.A., Williams, N.J., Sabo, E.F., Pluščec, J., Weaver, E.R., and Kocy, O., Angiotensin-Converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis, Biochemistry, 10, 4033, 1971.PubMedGoogle Scholar
  2. 2.
    Cheung, H.S. and Cushman, D.W., Inhibition of homogeneous angiotensin-convert-ing enzyme of rabbit lung by synthetic venom peptides of Bothrops jararaca, Biochem. Biophys. Acta, 293, 451, 1973.PubMedGoogle Scholar
  3. 3.
    Ondetti, M.A., Rubin, B., and Cushman, D.W., Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents, Science, 196, 441, 1977.PubMedGoogle Scholar
  4. 4.
    Laragh, J.H. and Sealey, J.E.,Therenin-angiotensin-aldosterone hormonal system and regulation of sodium, potassium and blood pressure homeostasis, in Handbook of Physiology, Sect. 8, Renal Physiology, Orloff, J. and Berliner, R.W., Eds., Amer. Physiol. Soc., Washington, D.C., 1973, 815.Google Scholar
  5. 5.
    Davis, J.O. and Freeman, R.H., Mechanisms regulating renin release, Physiol. Rev., 56, 1, 1976.PubMedGoogle Scholar
  6. 6.
    Ganten, D. and Gross, F., Interference with the renin-angiotensin system and their effects on high blood pressure, in Handbook of Experimental Pharmacology, Vol. 39, Antihypertensive Agents, Gross, F., Ed., Springer-Verlag, Berlin, 1977, chap. 11.Google Scholar
  7. 7.
    Peach, M.J., Renin-angiotensin system: biochemistry and mechanisms of action, Physiol. Rev., 57,313, 1977.PubMedGoogle Scholar
  8. 8.
    Vecsei, P., Hackenthal, E., and Ganten, D., The renin-angiotensin-aldosterone system, Klin. Wochenschr., 56 (Suppl. 1), 5, 1978.Google Scholar
  9. 9.
    Pisano, J.J. and Austen, K.F., Eds., Chemistry and biology of the kallikrein-kinin system in health and disease, U.S. Govt. Printing Office, Washington, D.C., DHEW Publication No. (NIH) 76-791, 1974, chap. 1-76.Google Scholar
  10. 10.
    Vane, J.R. and McGiff, J.C., Possible contributions of prostaglandins to the control of blood pressure, Circ. Res., 36/37, 1–68, 1975.Google Scholar
  11. 11.
    Carretero, O.A. and Scicli, A.G., The renal kallikrein-kinin system in human and in experimental hypertension, Klin. Vlochenschr., 56 (Suppl. 1), 113, 1978.Google Scholar
  12. 12.
    Dusting, G.J., Moncada, S., and Vane, J.R., Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems, Progr. Cardiovasc. Dis., 21, 405, 1979.Google Scholar
  13. 13.
    Nasjletti, A. and Malik, K.U., Relationships between the kallikrein-kinin and prostaglandin systems, Life Sci., 25, 99, 1979.PubMedGoogle Scholar
  14. 14.
    Cushman, D.W. and Ondetti, M.A., Inhibitors of angiotensin-converting enzyme, Progr. Med. Chem., 17, in press, 1980.Google Scholar
  15. 15.
    Erdös, E.G., Angiotensin I converting enzyme, Circ. Res., 36, 247, 1975.PubMedGoogle Scholar
  16. 16.
    Erdös, E.G., Commentary. The kinins, Biochem. Pharmacol., 25, 1563, 1976.PubMedGoogle Scholar
  17. 17.
    Erdös, E.G., Conversion of angiotensin I to angiotensin II, Am. J. Med., 60, 749, 1976.PubMedGoogle Scholar
  18. 18.
    Erdes, E.G., Ed., Handbook of Experimental Pharmacology, Vol. 25, Bradykinin, kallidin, and kallikrein, Springer-Verlag, Berlin, 1970, chap. 1-9.Google Scholar
  19. 19.
    Erdes, E.G., Ed., Handbook of Experimental Pharmacology, Vol. 25 Suppl., Bradykinin, kallidin, and kallikrein, Springer-Verlag, Berlin, 1979, chap. 1-17.Google Scholar
  20. 20.
    Page, I.H. and Bumpus, F.M., Eds., Handbook of Experimental Pharmacology, Vol. 37, Angiotensin, Springer-Verlag, Berlin, 1974, p. 1–519.Google Scholar
  21. 21.
    Ondetti, M.A. and Cushman, D.W., Inhibitors of the renin-angiotensin system, Annu. Rep. Med. Chem., 13, 82, 1978.Google Scholar
  22. 22.
    Cushman, D.W., Cheung, H.S., Sabo, E.F., Rubin, B., and Ondetti, M.A., Development of specific inhibitors of angiotensin I converting enzyme (kininase II), Fed. Proc, 38, 2778, 1979Google Scholar
  23. 23.
    Levinsky, N.G., The renal kallikrein-kinin system, Circ. Res., 44, 441, 1979.PubMedGoogle Scholar
  24. 24.
    McGiff, J.C. and Wong, P.Y-K, Compartmentalization of prostaglandins and prostacyclin within the kidney: implications for renal function, Fed. Proc., 38, 89, 1979.PubMedGoogle Scholar
  25. 25.
    Tigerstedt, R. and Bergman, P.G., Niere und Kreislauf, Skand. Arch. Physiol., 8, 223, 1898.Google Scholar
  26. 26.
    Goldblatt, H., Lynch, J., Hanzal, R.F., and Summerville, W.W., Studies on experimental hypertension. Production of persistent elevation of systolic blood pressure by means of renal ischemia, J. Exp. Med., 59, 347, 1934.PubMedGoogle Scholar
  27. 27.
    Braun-Menéndez, E.J., Fasciolo, J.C, Lelou, L.F., and Mñnoz, J.M., La substancia hipertensora de la sangre del riñon isquemiado, Rev. Soc. Arg. Biol., 15, 420, 1939.Google Scholar
  28. 28.
    Page, I.H. and Helmer, O.M., A crystalline pressor substance (angiotonin) resulting from the reaction between renin and renin activator, J. Exp. Med., 71, 29, 1940.PubMedGoogle Scholar
  29. 29.
    Braun-Menéndez, E.J. and Page, I.H., Suggested revision of nomenclature-angio-tensin, Science, 127, 242, 1958.PubMedGoogle Scholar
  30. 30.
    Skeggs, L.T., Marsh, W.H., Kahn, J.R., and Shumway, N.P., The existence of two forms of hypertensin, J. Exp. Med., 99, 275, 1954.PubMedGoogle Scholar
  31. 31.
    Lentz, K.E., Skeggs, L.T., Woods, K.R., Kahn, J.R., and Shumway, N.P., The amino acid composition of hypertensin II and its biochemical relationship to hypertension, J. Exp. Med., 104, 183, 1956.PubMedGoogle Scholar
  32. 32.
    Elliott, D.F. and Peart, W.S., The amino acid sequence in a hypertensin, Biochem J., 65, 246, 1957.PubMedGoogle Scholar
  33. 33.
    Skeggs, L.T., Lentz, K.E., Kehr, J.R., Shumway, N.P., and Woods, K.R., Amino acid sequence of hypertensin II, J. Exp. Med., 104, 193, 1956.PubMedGoogle Scholar
  34. 34.
    Schwyzer, R., Iselin, B., Kappeler, H., Rinker, B., Rittel, W., and Zuber, H., Syntheses von Hypertensin-peptiden, Chimie (Aarau), 11, 335, 1957.Google Scholar
  35. 35.
    Bumpus, F.M., Schwarz, H., and Page, I.H., Synthesis and pharmacology of the octapeptide angiotensin, Science, 125, 886, 1957.PubMedGoogle Scholar
  36. 36.
    Carpenter, C.C.J., Davis, J.O., and Ayers, C.R., Relation of renin, angiotensin II and experimental renal hypertension to aldosterone secretion, J. Clin. Invest., 40, 2026, 1961.PubMedGoogle Scholar
  37. 37.
    Genest, J., Biron, P., Koiw, E., Nowaczynski, W., Chretein, M., and Boucher R., Adrenocortical hormones in human hypertension and their relation to angiotensin, Circ. Res., 9, 775, 1961.PubMedGoogle Scholar
  38. 38.
    Gross, F., Renin und hypertensin, physiologische oder pathologische Wirkstoffe? Klin. Wochenschr., 36, 693, 1958.PubMedGoogle Scholar
  39. 39.
    Laragh, J.H., The role of aldosterone in man: evidence for regulation of electrolyte balance and arterial pressure by renal-adrenal system which may be involved in malignant hypertension, J. Am. Med. Assoc., 174, 293, 1960.Google Scholar
  40. 40.
    Mulrow, P.J., Ganong, W.F., Cera, G., and Kuljian, A., Nature of aldosterone stimulating factors in dog kidneys, J. Clin. Invest., 41, 505, 1962.PubMedGoogle Scholar
  41. 41.
    Ng, K.K.F. and Vane, J.R., Conversion of angiotensin I to angiotensin II, Nature, 216, 762, 1967.PubMedGoogle Scholar
  42. 42.
    Blair-West, J.R., Coghlan, J.P., Denton, D.A., Funder, J.W., Scoggins, B.A. and Wright, R.D., The effect of the heptapeptide (2-8) and the hexapeptide (3-8) fragments of angiotensin II on aldosterone secretion, J. Clin. Endocrinol. Metab., 32, 575, 1971.PubMedGoogle Scholar
  43. 43.
    Goodfriend, T.L. and Peach, M.J., Angiotensin III; (des-aspartic acid )-angio-tensin II. Evidence and speculation for its role as an important agonist in the renin-angiotensin system. Circ. Res., 36/37, 1–38, 1975..Google Scholar
  44. 44.
    McCaa, R.E., Aldosterone response to long term infusion of angiotensin II and angiotensin III in conscious dogs before and after dietary sodium restriction, Endocrinology, 103, 458, 1978.PubMedGoogle Scholar
  45. 45.
    Werle, E., Discovery of the most important kallikreins and kallikrein inhibitors, in Handbook of Experimental Pharmacology, Vol. 25, Bradykinin, Kallidin and Kallikrein, Erdes, E.G., Ed., Springer-Verlag, Berlin, 1970, chap. 1.Google Scholar
  46. 46.
    Eisen, V. and Vogt, W., Plasma kininogenases and their activators, in Handbook of Experimental Pharmacology, Vol. 25, Bradykinin, Kallidin and Kallikrein, Erdos, E.G., Ed., Springer-Verlag, Berlin, 1970, chap. 3.Google Scholar
  47. 47.
    Webster, M.E., Kallikreins in glandular tissues; recommendations for nomenclature and units, in Handbook of Experimental Pharmacology, Vol. 25, Bradykinin, Kallidin and Kallikrein, Erdös, E.G., Ed., Springer-Verlag, Berlin, 1970, p. 131 and p. 659.Google Scholar
  48. 48.
    Rocha e Silva, M., Beraldo, W.T., and Rosenfeld, G., Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin, Am. J. Physiol., 156, 261, 1949.Google Scholar
  49. 49.
    Elliott, D.F., Horton, E.W., and Lewis, G.P., Actions of pure bradykinin, J. Physiol., 153, 473, 1960.PubMedGoogle Scholar
  50. 50.
    Boissonnas, R.A., Guttman, S., and Jaquenod, P.A., Synthese de la L-arginyl-L-prolyl-L-prolyl-glycyl-L-phenylalanyl-L-seryl-L-prolyl-L-phénylalanyl-L-arginine, un nonapeptide Drésentant les propriétés de la bradykinine, Helv. chem. Acta, 43, 1349, 1960.Google Scholar
  51. 51.
    Igic, R., Erdös, E.G., Yeh, H.S.J., Sorelic, K., and Nakajima, T., Angiotensin I converting enzyme of the lung, Cire. Res., 30/31, 11–51, 1972.Google Scholar
  52. 52.
    Ferreira, S.H., A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca, Brit. J. Pharmacol., 24, 163, 1965.PubMedGoogle Scholar
  53. 53.
    Bakhle, Y.S., Conversion of angiotensin I to angiotensin II by cell-free extracts of dog lung, Nature, 220, 919, 1968.PubMedGoogle Scholar
  54. 54.
    Ferreira, S.H., Bartelt, D.C., and Greene, L.J., Isolation of bradykinin potentiating peptides from Bothrops jararaca venom, Biochemistry, 9, 2583, 1970.PubMedGoogle Scholar
  55. 55.
    Ferreira, S.H., Greene, L.J., Alabaster, V.A., Bakhle, Y.S., and Vane, J.R., Activity of various fractions of bradykinin potentiating factor against angio-tensin-converting enzyme, Nature, 225, 379, 1970.PubMedGoogle Scholar
  56. 56.
    Stewart, J.M., Ferreira, S.H., and Greene, L.J., Bradykinin potentiating peptide PCA-Lys-Trp-Ala-Pro. An inhibitor of the pulmonary inactivation of bradykinin and conversion of angiotensin I to II, Biochem. Pharmacol., 20, 1557, 1971.Google Scholar
  57. 57.
    Cushman, D.W. and Cheung, H.S., Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung, Biochem. Pharmacol., 20, 1637, 1971.Google Scholar
  58. 58.
    Engel, S.L., Schaeffer, T.R., Gold, B.I., and Rubin, B., Inhibition of pressor effects of angiotensin I and augmentation of depressor effects of bradykinin by synthetic peptides, Proc. Soc. Exp. Biol. Med., 140, 240, 1972.PubMedGoogle Scholar
  59. 59.
    O’Keefe, E.H., Kotier, D.G., Waugh, M.H., and Rubin, B., Inhibition and augmentation by peptide SQ 20,881 of contractile effects of angiotensin I (AI) and of bradykinin (B), respectively, on excised smooth muscle, Fed. Proc., 31, 511, 1972.Google Scholar
  60. 60.
    Kato, H. and Suzuki, T., Bradykinin-potentiating peptides from the venom of Agkistrodon halys blomhoffii. Isolation of five bradykinin potentiators and the amino acid sequence of two of them, potentiators B and C, Biochemistry, 10, 972, 1971.PubMedGoogle Scholar
  61. 61.
    Bakhle, Y.S., Inhibition of converting enzyme by venom peptides, in Hypertension, Genest, J. and Koiw, E., Eds., Springer-Verlag, Berlin, 1972, p. 541.Google Scholar
  62. 62.
    Greene, L.J., Camargo, A.C.M., Krieger, E.M., Stewart, J.M., and Ferreira, S.H., Inhibition of the conversion of angiotensin I to II and potentiation of bradykinin by small peptides present in Bothrops jararaca venom, Circ. Res., 30/31, 11–62, 1972.Google Scholar
  63. 63.
    Engel, S.L., Schaeffer, T.R., Waugh, M.H., and Rubin, B., Effects of the nona-peptide SQ 20,881 on blood pressure of rats with experimental hypertension, Proc. Soc. Exp. Biol. Med., 143, 483, 1973.PubMedGoogle Scholar
  64. 64.
    Muirhead, E.E., Brooks, B., and Arora, K.K., Prevention of malignant hypertension by the synthetic peptide SQ 20,881, Lab. Invest., 30, 129, 1974.Google Scholar
  65. 65.
    Collier, J.G., Robison, B.F., and Vane, J.R., Reduction of pressor effects of angiotensin I in man by synthetic nonapeptide which inhibits converting enzyme, Lancet, 1, 72, 1973.PubMedGoogle Scholar
  66. 66.
    Gavras, H., Brunner, H.R., Laragh, J.H., and Vukovich, R.A., An angiotensin converting enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients, N.Engl. J. Med., 291, 817, 1974.PubMedGoogle Scholar
  67. 67.
    Johnson, J.G., Black, W.D., Vukovich, R.A., Hatch, F.E., Jr., Friedman, B.I., Blackwell, C.F., Shenouda, A., Share, L., Shade, R.E., Acchiardo, S.R., and Muirhead, E.E., Treatment of patients with severe hypertension by inhibition of angiotensin-converting enzyme, Clin. Sci. Mol. Med., 48, 53s, 1975.Google Scholar
  68. 68.
    Case, D.B., Wallace, J.M., Keim, H.J., Weber, M.A., Sealey, J.E., and Laragh, J.H., Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme, N. Engl. J. Med., 206, 641, 1977.Google Scholar
  69. 69.
    Krieger, E.M., Salgado, H.C., Assan, C.J., Greene, L.J., and Ferreira, S.H., Potential screening test for detection of overactivity of the renin-angiotensin system, Lancet, 1, 269, 1971.PubMedGoogle Scholar
  70. 70.
    Cushman, D.W., Cheung, H.S., Sabo, E.F., and Ondetti, M.A., Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids, Biochemistry, 16, 5484, 1977.PubMedGoogle Scholar
  71. 71.
    Rubin, B., O’Keefe, E.H., Kotler, D.O., DeMaio, D.A., and Cushman, D.W., Use of excised guinea pig ileum as a predictive test for inhibitors in vivo of angiotensin-converting enzyme (ACE), Fed. Proc., 34, 770, 1975.Google Scholar
  72. 72.
    Rubin, B., Laffan, R.J., Kotler, D.G., O’Keefe, E.H., DeMaio, D.A., and Goldberg, M.E., SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline), a novel orally active inhibitor of angiotensin-converting enzyme, J. Pharmacol. Exp. Ther. 204, 271, 1978.PubMedGoogle Scholar
  73. 73.
    Rubin, B., Antonaccio, M.J., and Horovitz, Z.P., captopril (SQ 14,225) (D-3-mercapto-2-methylpropanoyl-L-proline): a novel orally active inhibitor of angiotensin-converting enzyme and antihypertensive agent, Progr. Cardiovasc. Dis., 21, 183, 1978.Google Scholar
  74. 74.
    Harris, D.N., Heran, C.L., Goldenberg, H.J., High, J.P., Laffan, R.J., Rubin, B., Antonaccio, M.J., and Goldberg, M.E., Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs, Eur. J. Pharmacol., 51, 345, 1978.PubMedGoogle Scholar
  75. 75.
    Murthy, V.S., Waldron, T.L., Goldberg, M.E., and Vollmer, R.R., Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits, Eur. J. Pharmacol 46, 207, 1977.PubMedGoogle Scholar
  76. 76.
    Murthy, V.S., Waldron, T.L., and Goldberg, M.E., The mechanism of bradykinin potentiation after inhibition of angiotensin-converting enzyme by SQ 14,225 in conscious rabbits, Circu. Res., 43, 1–40, 1978.Google Scholar
  77. 77.
    Rubin, B., Duchin, K.L., and Antonaccio, M.J., Effects of chronic captopril (C) on renal function and vascular reactivity in conscious Wistar-Kyoto (WKY) rats, Fed. Proc, 38, 851, 1979.Google Scholar
  78. 78.
    Murthy, V.S., Waldron, T.L., and Goldberg, M.E., Inhibition of angiotensin converting enzyme by SQ 14,225 in anesthetized dogs: hemodynamic and renal vascular effects, Proc. Soc. Exp. Biol. Med., 157, 121, 1978.PubMedGoogle Scholar
  79. 79.
    Vollmer, R.R. and Boccagno, J.A., Central cardiovascular effects of SQ 14,225, an angiotensin-converting enzyme inhibitor in chloralose-anesthetized cats, Eur. J. Pharmacol., 45, 117, 1977.PubMedGoogle Scholar
  80. 80.
    Ferguson, R.K., Brunner, H.R., Turini, G.A., Gavras, H., and McKinstry, D.N., A specific orally active inhibitor of angiotensin-converting enzyme in man, Lancet, 1, 775, 1977.PubMedGoogle Scholar
  81. 81.
    Bing, J. and Poulsen, K., Time course of changes in plasma renin after blockade of the renin system, Acta Path. Microbiol, scand., Sect. A, 83, 454, 1975.Google Scholar
  82. 82.
    Haber, E., Sancho, J., Re, R., Burton, J., and Barger, A.C., The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal man, Clin. Sci. Mol. Med., 48, 495, 1975.Google Scholar
  83. 83.
    Samuels, A.I., Miller, Jr.,E.D., Fray, J.C.S., Haber, E.,and Barger, A.C.,Renin-angiotensin antagonists and the regulation of blood pressure, Fed. Proc, 35, 2512, 1976.PubMedGoogle Scholar
  84. 84.
    Thurston, H. and Laragh, J.H., Prior receptor occupancy as a determinant of the pressor activity of infused angiotensin II in the rat, Circ. Res., 36, 113, 1975.PubMedGoogle Scholar
  85. 85.
    Laffan, R.J., Goldberg, M.E., High, J.P., Schaeffer, T. R., Waugh, M.H., and Rubin, B., Antihypertensive activity in rats of SQ 14,225, an orally active inhibitor of angiotensin converting enzyme, J. Pharmacol. Exp. Ther., 204, 281, 1978.PubMedGoogle Scholar
  86. 86.
    Bengis, R.G., Coleman, T.G., Young, D.B., and McCaa, R.E., Long-term blockade of angiotensin formation in various normotensive and hypertensive rat models using converting enzyme inhibitor (SQ 14,225), Circ. Res., 43 (Suppl. I),45, 1978.Google Scholar
  87. 87.
    Jaeger, P., Ferguson, R. K., Brunner, H.R., Kirchertz, R., and Gavras, H., Mechanism of blood pressure reduction by teprotide (SQ 20,881) in rats, Kidney Int., 13, 289, 1978.PubMedGoogle Scholar
  88. 88.
    Vollmer, R.R., Boccagno, J.A., Harris, D.N., and Murthy, V.S., Hypotension induced by inhibition of angiotensin-converting enzyme in pentobarbital-anesthetized dogs, Eur. J. Pharmacol., 51, 39, 1978.PubMedGoogle Scholar
  89. 89.
    McCaa, R.E., Hall, J.E.,and McCaa, C.S., The effects of angiotensin I-con-verting enzyme inhibitors on arterial blood pressure and urinary sodium excretion. Role of the renin-angiotensin and kallikrein-kinin systems, Circ. Res., 43 (Suppl. I), 32, 1978.Google Scholar
  90. 90.
    McCaa, R.E., McCaa, C.S., Bengis, R.G., and Guyton, A.C., Role of aldosterone in experimental hypertension, J. Endocrinol., 81, 69P, 1979.Google Scholar
  91. 91.
    Antonaccio, M.J., Rubin, B., Horovitz, Z.P., Mackaness, G., and Panasevich, R., Long-term efficacy of captopril (SQ 14,225) in 2-kidney renal hypertensive rats. Clin. Exp. Hypertension, 1, 505, 1979.Google Scholar
  92. 92.
    Brown, T.C, Davis, J.O., Olichney, M.J., and Johnston, C.I., Relation of plasma renin to sodium balance and arterial pressure in experimental renal hypertension, Circ. Res., 18, 475, 1966.PubMedGoogle Scholar
  93. 93.
    Gavras, H., Oliver, J.A.,and Cannon, P.J., Interrelations of renin, angioten sin II, and sodium in hypertension and renal failure, Annu. Rev. Med., 27, 485, 1976.PubMedGoogle Scholar
  94. 94.
    Mikoche, L.W., Miksche, U., and Gross, F., Effect of sodium restriction on renal hypertension and on renin activity in the rat, Circ. Res., 27, 973, 1970.Google Scholar
  95. 95.
    Rubin, B., Antonaccio, M.J., Goldberg, M.E., Harris, D.M., Itkin, I.G., Horovitz, Z.P., Panasevich, R.E., and Laffan, R.J., Chronic antihyperten sive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor in conscious 2-kidney renal hypertensive rats, Eur. J. Pharmacol., 51, 377, 1978.PubMedGoogle Scholar
  96. 96.
    Douglas, J.R., Jr., Johnson, E.M., Jr., Heist, J.F., Marshall, G.R., and Needleman, P., Is the peripheral sympathoadrenal nervous system necessary for renal hypertension?, J. Pharmacol. Exp. Ther., 196, 35, 1976.PubMedGoogle Scholar
  97. 97.
    Thurston, H. and Swales, J.D., Blood pressure response of nephrectomized hypertensive rats to converting enzyme inhibition: Evidence for persistent vascular renin activity, Clin. Sci. Mol. Med., 52, 299, 1977.PubMedGoogle Scholar
  98. 98.
    Riegger, A.J.G., Lever, A.F., Millar, J.A., Morton, J.J.,and Slack, B., Correction of renal hypertension in rat by long term infusion of angiotensin inhibitors, Lancet, 2, 1317, 1977.PubMedGoogle Scholar
  99. 99.
    Gavras, H., Brunner, H.R., Laragh, J.H., Gavras, I., and Vukovich, R. A., The use of angiotensin converting enzyme inhibitor in the. diagnosis and treatment of hypertension, Clin. Sci. Mol. Med., 48, 57S, 1975.Google Scholar
  100. 100.
    Sen, S., Smeby, R. R., Bumpus, F.M., and Turcotte, R.G., Role of renin-angiotensin system in chronic renal hypertensive rats, Hypertension, 1, 427, 1979.PubMedGoogle Scholar
  101. 101.
    Freeman, R.H., Davis, J.O., Watkins, B.E., Stephens, G.A., and DeForrest, J.M., Effects of continuous converting enzyme blockade on renovascular hypertension in the rat, Am. J. Physiol., 236, F21, 1979.PubMedGoogle Scholar
  102. 102.
    Watkins, B.E., Davis, J.O., Freeman, R.H., Stephens, G.A.,and DeForrest, J.M. Effects of oral converting enzyme inhibitor (SQ 14,225) on one-kidney hypertension in the dog, Proc. Soc. Exp. Biol. Med., 157, 245, 1978.PubMedGoogle Scholar
  103. 103.
    Watkins, B.E., Davis, J.O., Freeman, R.H., DeForrest, J.M.,and Stephens, G.A., Continuous angiotensin II blockade throughout the acute phase of one-kidney hypertension in the dog, Circ. Res., 42, 813, 1978.PubMedGoogle Scholar
  104. 104.
    Miller, E.D., Jr., Samuals, A.I., Haber, E., and Barger, A.C., Inhibition of angiotensin conversion in experimental renovascular hypertension, Science, 177, 1108, 1972.PubMedGoogle Scholar
  105. 105.
    Ayers, C.R., Vaughan, E.D., Jr., Yancey, M.R., Bing, K.T., Johnson, C.C., and Morton, C, Effect of l-sarcosine-8-alanine angiotensin II and converting enzyme inhibitor on renin release in dog acute renovascular hypertension, Circ. Res., 34, 127, 1974.Google Scholar
  106. 106.
    Muirhead, E.E., Brooks, B.,and Arora, K.K., Prevention of malignant hypertension by the synthetic peptide SQ 20,881, Lab. Invest., 30, 129, 1974.Google Scholar
  107. 107.
    Svendsen, U.G., Effects of the nonapeptide (SQ 20,881) on the blood pressure of conscious normotensive and chronic hypertensive mice, Acta Path. Microbiol. Scand., Sect. A, 85, 942, 1977.Google Scholar
  108. 108.
    Watanabe, T.X. and Sokabe, H., Acute vasodepressor effect of D-3-mercapto-2-methyl-propanoyl-L-proline (SQ 14,225) in the stroke-prone substrain of spontaneously hypertensive rats (SHRSP), Jap. J. Pharmacol., 29, 133, 1979.PubMedGoogle Scholar
  109. 109.
    Antonaccio, M.J., Rubin, B., Horovitz, Z.P., Laffan, R.J., Goldberg, M.E., Harris, D.N., and Zaidi, I. Effects of chronic treatment with Captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats, Jap. J. Pharmacol., 29, 285, 1979.PubMedGoogle Scholar
  110. 110.
    Ferrone, R.A. and Antonaccio, M.J., Prevention of the development of spontaneous hypertension in rats by captopril (SQ 14,225), Eur. J. Pharmacol., In press.Google Scholar
  111. 111.
    Douglas, B.H., Langford, H.C., and McCaa, R.E., Response of mineralocorti-coid hypertensive animals to an angiotensin I converting enzyme inhibitor, Proc. Soc. Exp. Biol. Med., 161, 86, 1979.PubMedGoogle Scholar
  112. 112.
    Atlas, S.A., Case, D.B., Sealey, J.E., McKinstry, D.N., and Laragh, J.H., Blunted aldosterone secretion, natriuresis and potassium retention during chronic aldosterone blockade in hypertensive patients, Clin. Res., 26, 361A, 1978.Google Scholar
  113. 113.
    Atlas, S.A., Case, D.B. Sealey, J.E., Sullivan, P.M., and Laragh, J.H., Involvement of the renin-angiotensin-aldosterone axis in the antihypertensive action of captopril (SQ 14,225), Circulation, 57/78 (Suppl. II), 11–143, 1978.Google Scholar
  114. 114.
    Case, D.B., Atlas, S.A., Laragh, J.H., Sealey, J.E., Sullivan, P.A., and McKinistry, D.N., Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting-enzyme inhibitor (SQ 14,225, Captopril) in hypertensive patients, Prog. Cardiovasc. Dis., 21, 195, 1978.PubMedGoogle Scholar
  115. 115.
    Atlas, S.A., Case, D.B., Sealey, J.E., Laragh, J.H., and McKinstry, D.N., Interruption of the renin-angiotensin system in hypertensive patients by captopril induces sustained reduction in aldosterone secretion, potassium retention and natriuresis, Hypertension, 1, 274, 1979.PubMedGoogle Scholar
  116. 116.
    Cody, R.J.,Jr., Tarazi, R.C., Bravo, E.L., and Fouad, F.M., Hemodynamics of orally-active converting enzyme inhibitor (SQ 14,225) in hypertensive patients. Clin. Sci. Mol. Med., 55, 453, 1978.PubMedGoogle Scholar
  117. 117.
    Brunner, H. R., Gavras, H., Waeber, B., Kershaw, G.R., Turini, G.A., Vuko-vich, R.A., and McKinstry, D.N., Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients, Ann. Intern. Med., 90, 19, 1979.PubMedGoogle Scholar
  118. 118.
    Brunner, H.R., Gavras, H., Turini, G.A., Waeber, B., and Wauters, J.P., Long-term angiotensin blockade in hypertensive patients with chronic renal failure Clin. Res., 26, 459A, 1978.Google Scholar
  119. 119.
    Brunner, H.R., Waeber, B., Wauters, J.P., Turini, G., McKinstry, D., and Gavras, H., Inappropriate renin secretion unmasked by captopril (SQ 14,225) in hypertension of chronic renal failure, Lancet, 2, 704, 1978.PubMedGoogle Scholar
  120. 120.
    Baker, K.M. Vaughn, E.D., Jr., Johns, D.W., Ayers, C.R., and Carey, R.M., Antihypertensive effects of angiotensin blockade: SQ 14,225 versus P113, Clin. Res., 26, 779A, 1978.Google Scholar
  121. 121.
    Bravo, E. L. and Tarazi, R.C., Converting enzyme inhibition with an orally active compound in hypertensive man, Hypertension, 1, 39, 1979.PubMedGoogle Scholar
  122. 122.
    Gavras, H., Brunner, H.R., Turini, G.A., Kershaw, G.R., Tifft, C.P., Cutte-lod, S., Gavras, I., Vukovich, R.A., and McKinstry, D.N., Antihypertensive effect of the oral angiotensin converting enzyme inhibitor SQ 14,225 in man, N. Engl. J. Med., 298, 991, 1978.PubMedGoogle Scholar
  123. 123.
    Sullivan, J.M., Ginsburg, B.A., Ratts, T.E., Johnson, J.G., Barton, B.A., Kraus, D.H., McKinstry, D.N., and Muirhead, E.E., Hemodynamic and antihypertensive effects of Captopril, an orally active angiotensin converting enzyme inhibitor, Hypertension, 1, 397, 1979.PubMedGoogle Scholar
  124. 124.
    Favre, L., Frazer, M., McKinstry, D.N., and Hollifield, J.W., Chronic antihypertensive therapy with an oral converting-enzyme inhibitor (CEI), Circulation, 57/58 (Suppl. II), 1–57, 1978.Google Scholar
  125. 125.
    McKinstry, D.N., Willard, D.A., and Vukovich, R.A., Antihypertensive and hormonal effects of the converting enzyme inhibitor, Captopril, alone or combined with hydrochlorothiazide, Clin. Pharmacol. Ther., 25, 237, 1979.Google Scholar
  126. 126.
    Ferrone, R.A. and Heran, C.L., Hemodynamic effects of SQ 14,225 and guanethi-dine in spontaneously hypertensive rats. Circulation, 57/58 (Suppl. II), 11–144, 1978.Google Scholar
  127. 127.
    Muirhead, E. E., Prewitt, R. L., Jr., Brooks, B., and Brosius, W. L., Jr., Antihypertensive action of the orally active converting enzyme inhibitor (SQ 14,225) in spontaneously hypertensive rats, Circ. Res. (Suppl. I), 43: 153, 1978.Google Scholar
  128. 128.
    Duchin, K. L. and Steinbacher, T.E., Effects of captopril (SQ 14,225) on renal function in the dog. Kidney Int., 14, 693, 1978.Google Scholar
  129. 129.
    Ondetti, M.A. and Cushman, D.W., Angiotensin-Converting Enzyme Inhibitors, in The Biochemical Regulation of Blood Pressure. Soffer, R.L., Ed., John Wiley and Sons, New York, In press.Google Scholar
  130. 130.
    Antonaccio, M.J., Harris, D., Goldenberg, H., High, J.P.,and Rubin, B., The effects of Captopril, propranolol, and indomethacin on blood pressure and plasma renin activity in spontaneously hypertensive and normotensive rats, Proc. Soc. Exp. Biol. Med., In press.Google Scholar
  131. 131.
    Brunner, H.R., Gavras, H.,and Laragh, J.H., Hypertension in man. Exposure of the renin and sodium components using angiotensin II blockade. Circ Res. 34/35 (Suppl. I), 135, 1974.Google Scholar
  132. 132.
    Pettinger, W.A. and Mitchell, H.C., Renin release, saralasin, and the vasodilator-beta blocker drug interaction in man, N. Engl. J. Med., 292, 1214, 1975.Google Scholar
  133. 133.
    Atkinson, A.B., Brown, J.J., Lever, A.F., Morton, J.J., Frazer, R., and Robertson, J.I.S., Changes in plasma angiotensin II during captopril therapy in renal hypertension and intractable essential hypertension. Proceedings of the 6th Scientific Meeting of the International Society on Hypertension, Göteborg, June 11-13, p. 121, 1979.Google Scholar
  134. 134.
    Matthews, 6., McGrath, B.,and Johnston, C, Hormonal changes with long-term converting enzyme inhibition by captopril in essential hypertension, Proceedings of the 6th Scientific Meeting of the International Society on Hypertension, Göteborg, June 11-13, p. 156, 1979.Google Scholar
  135. 135.
    Millar, J.A., and Johnston, C.I., The effect of captopril (SQ 14,225) on circulating levels and clearance of angiotensin I and bradykinin in man, dog, and rabbit, Proceedings of the 6th Scientific Meeting of the International Society on Hypertension, Goteborg, June 11-13, p. 157, 1979.Google Scholar
  136. 136.
    Keim, H.J., Bindel, G., Distler, A., Fleckenstein, P.,and Cordes, U., Long-term treatment of essential hypertension (EH) with the oral converting enzyme inhibitor SQ 14,225, Proceedings of the 6th Scientific Meeting of the International Society on Hypertension, Goteborg, June 11-13, p. 144, 1979.Google Scholar
  137. 137.
    McKinstry, D.N., Singhvi, S.M., Kripalani, K.J., Dreyfuss, J., Willard, D.A., and Vukovich, R.A., Disposition and cardiovascular-endocrine effects of an orally active angiotensin-converting enzyme inhibitor, SQ 14,225, in normal subjects, Clin. Pharmacol. Ther., 23, 121, 1978.Google Scholar
  138. 138.
    Crofton, J.T., Share, L.,and Horovitz, Z.P., The effect of SQ 14,225 on systolic blood pressure and urinary excretion of vasopressin in the developing SH rat. Hypertension, 1, 462, 1979.PubMedGoogle Scholar
  139. 139.
    Johnson, J.A. and Davis, J.O., Effects of a specific competitive antagonist of angiotensin II on arterial pressure and adrenal steroid secretion in the dog, Circ. Res., 32 (Suppl. I), 1159, 1973.Google Scholar
  140. 140.
    Watkins, L.J., Burton, J.A., Huber, E., Cant, T.R., Smith, F.W., and Bar-ger, A.C., The renin-angiotensin system in congestive failure in conscious dogs, J. Clin. Invest., 57, 1606, 1976.PubMedGoogle Scholar
  141. 141.
    Freeman, R.H., Davis, J.O., Williams, G.M., DeForrest, J.M., Seymour, A.A., and Rowe, B.P., Effects of the oral converting enzyme inhibitor, SQ 14,225, in a model of low cardiac output in dogs, Circ. Res., 45, 540, 1979.PubMedGoogle Scholar
  142. 142.
    Williams, G.M., David, J.O., Freeman, R.H., DeForrest, J.M., Seymour, A.A., and Rowe, B.P. Effects of the oral converting enzyme inhibitor, SQ 14,225, in experimental high output failure, Am. J. Physiol., 236, F541, 1979.PubMedGoogle Scholar
  143. 143.
    Adler, R., Chatterjee, K., Ports, T., Hiramatsu, B.,and Parmley, W., Beneficial hemodynamic effects of angiotensin converting enzyme inhibitor in chronic refractory heart failure, Am. J. Cardiol., 43, 404, 1979.Google Scholar
  144. 144.
    Davis, R., Ribner, H.S., Keung, E., Sonnenblick, E.H., and LeJemtel, T.H., Treatment of chronic congestive heart failure with captopril, an oral inhibitor of angiotensin-converting enzyme, N. Engl. J. Med., 301, 117, 1979.PubMedGoogle Scholar
  145. 145.
    Turini, G.A., Gribic, M., Brunner, H.R., Waeber, B.,and Gavras, H., Improvement of chronic congestive heart failure by oral captopril, Lancet, 1, 1213, 1979.PubMedGoogle Scholar
  146. 146.
    Mason, D.T., Awan, N.A., Hennanovich, J. and Joye, O.A., Oral captopril in congestive heart failure: efficacy by cardiac catherization, forearm plethysmography, nuclear scintigraphy, echography, treadmill exercise symptoms, Circulation, 59/60 (Suppl. II), 230, 1979.Google Scholar
  147. 147.
    Levine, T.B., Carlyle, P.F., Gross, K.A., Franciosa, J.A. and Cohn, J.A., Hemodynamic and clinical response to captopril in congestive heart failure, Circulation, 59/60 (Suppl. II), 39, 1979.Google Scholar
  148. 148.
    Halperin, J.L., Creager, M.A., Faxon, D.P., Gavras, H, and Ryan, T.J., Chronic oral angiotensin inhibition for the treatment of refractory heart failure, Circulation, 59/60 (Suppl. II), 39, 1979.Google Scholar
  149. 149.
    Fouad, F.M., Cerino, J.M., Tarazi, R.C. and Bravo, E.L., Converting enzyme inhibition (CEI) in normotensive heart failure (HF): long term hemodynamic and humoral effects, Circulation, 59/60 (Suppl. II), 130, 1979.Google Scholar
  150. 150.
    Fouad, F.M., Cerino, J.M., Tarazi, R.C. and Bravo, E.L., Oral converting enzyme inhibitor in resistant heart failure, Clin. Res., 27, 673A, 1979.Google Scholar
  151. 151.
    Trache, G.J. and Lefer, A.M., Beneficial action of a new angiotensin-con-verting enzyme inhibitor (SQ 14,225) in hemorrhagic shock in cats, Cire. Res., 43, 576, 1978.Google Scholar
  152. 152.
    Hollenberg, N.K., Williams, G.H., Adams, D.F., Moore, T., Brown, C, Borucki, L.J Leung, F., Booli, S., Solomon, H.S., Passau, D. and Dluhy, R., Pharmacological interruption of the renin-angiotensin system, Medicine, 58, 115, 1979.PubMedGoogle Scholar
  153. 153.
    Carretero, O.A. and Gulati, O.P., Effects of angiotensin antagonist in rats with acute, subacute, and chronic two-kidney renal hypertension, J. Lab. Clin. Med., 91, 264, 1978.PubMedGoogle Scholar
  154. 154.
    Koletsky, S., Rivera-Velez, J.M., Marsh, D.G., and Pritchard, W.H., Relation of renal arterial pressure to activity of renin-angiotensin system in renal hypertension, Proc. Soc. Exp. Biol. Med., 125, 96, 1967.PubMedGoogle Scholar
  155. 155.
    Koletsky, S. and Rivera-Velez, J.M., Factors determining the success or failure of nephrectomy in experimental renal hypertension, J. Lab. Clin. Med., 76., 54, 1970.PubMedGoogle Scholar
  156. 156.
    Shiono, K. and Sokabe, H., Renin-angiotensin system in spontaneously hypertensive rats, Am. J. Physiol., 231, 1295, 1976.PubMedGoogle Scholar
  157. 157.
    Pals, D.T., Masucci, F.D., Denning, G.S., Jr., Sipos, F., and Fessier, D.C., Role of the pressor action of angiotensin II in experimental hypertension, Circ. Res., 29, 673, 1971.PubMedGoogle Scholar
  158. 158.
    Miyazaki, M. and Yamamoto, K., Synthetic phosphatidyl-ethanolamines as renin inhibitors, Proc. Soc. Exp. Biol. Med., 155, 468, 1977.PubMedGoogle Scholar
  159. 159.
    Horovitz, Z.P., Pharmacology and mechanism of action of inhibitors of the angiotensin converting enzyme in Pharmacology and Clinical Use of Angiotensin I Converting Enzyme Inhibitors, Drug Development and Evaluation, voll 4. Gross, F. and Liedtke, R.K., Eds., Gustav Fischer Verlag, Stuttgart, 1980, p. 9–14.Google Scholar
  160. 160.
    Ganten, D., Hutchinson, J.S., Schelling, P., Ganten, U.,and Fischer, H., The iso-renin angiotensin systems in extrarenal tissue, Clin. Exp. Pharmacol. Physiol., 3, 103, 1976.PubMedGoogle Scholar
  161. 161.
    Swales, J.D., Arterial wall or plasma renin in hypertension, Clin. Sci., 56, 293, 1979.PubMedGoogle Scholar
  162. 162.
    Sen, S., Smeby, R. R., and Bumpus, F.M., Renin in rats with spontaneous hypertension, Circ. Res., 31, 876, 1972.PubMedGoogle Scholar
  163. 163.
    Asaad, M.M. and Antonaccio, M.J., The effects of captopril (SQ 14,225) on vascular tissue renin in spontaneously hypertensive (SHR) and WKY-normotensive (NTR) rats: Relationship to systolic blood pressure (SBP) and plasma renin activity (PRA), Pharmacologist, 21, 212, 1979.Google Scholar
  164. 164.
    Aoki, K., Experimental studies on the relationship between endocrine organs and hypertension in spontaneously hypertensive rats. III. Role of the endocrine organs and hormones, Jap. Heart J., 5, 57, 1964.Google Scholar
  165. 165.
    Okamoto, K. and Aoki, K., Development of a strain of spontaneously hypertensive rats, Jap. Cire. J., 27, 282, 1963.Google Scholar
  166. 166.
    Swales, J.D., Antagonists, inhibitors and antisera in the evaluation of vascular renin activity. In: Progress in Biochemical Pharmacology. Vol. 12: Drugs Affecting the Renin-Angiotensin-Aldosterone System. Use of Angiotensin Inhibitors, edited by G.S. Stokes and K.D.G. Edwards, pp. 98–113, S. Karger, New York.Google Scholar
  167. 166a.
    Antonaccio, M.J., Rubin, B.,and Horovitz, Z.P., Effects of captopril in animal models of hypertension, Clin. Exp. Hypertension, In press.Google Scholar
  168. 167.
    Margolius, H.S., Geller, R., DeJong, W., Pisano, J.J., and Sjoerdsma, A., Altered urinary kallikrein excretion in rats with hypertension, Circ. Res. 30, 358, 1972.PubMedGoogle Scholar
  169. 168.
    Waeber, B., Brunner, H.R., Turini, G.A., Curtet, N., and Gavras, H., Blood pressure control by captopril despite intermittent normalization of angiotensin converting enzyme activity, Clin. Res., 27, 319A, 1979.Google Scholar
  170. 169.
    McCarthy, D.A., Potter, D.E., and Nicolaides, E.D., An in vivo estimation of of the potencies and half-lives of synthetic bradykinin and kallidin, J. Pharmacol. Exp. Ther., 148, 117, 1965.PubMedGoogle Scholar

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