The Biological Production of Angiotensin

  • Leonard T. Skeggs
  • Frederic E. Dorer
  • Joseph R. Kahn
  • Kenneth E. Lentz
  • Melvin Levine
Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 37)


The reaction of kidney renin with its plasma substrate to form angiotensin has been studied for many years using both crude and purified materials derived from many species. Much effort has been expended in the attempt to show the existence or efficacy of inhibitors or activators of the reaction. Many enzymological studies have been carried out to determine optimum pH, Michaelis constants, and maximal velocities. Much of the work prior to 1968 has been reviewed in a publication edited by Page and McCubbin (1968).


Renin Activity Renin Inhibitor Human Renin Renin Substrate Homologous Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson, R. C., Herbert, P. N., Mulrow, P. J.: A comparison of properties of renin obtained from the kidney and uterus of the rabbit. Amer. J. Physiol. 215, 774 (1968).PubMedGoogle Scholar
  2. Arakawa, K., Nakamura, M.: Studies on human angiotensin. Circulât. Res. 20–21 (Suppl. II), 101 (1967).Google Scholar
  3. Blaquier, P.: Kinetic studies of renin-angiotensinogen reaction after nephrectomy. Amer. J. Physiol. 208, 1083 (1965).PubMedGoogle Scholar
  4. Braun-Menendez, E., Fasciolo, J. C., Leloir, L. F., Mtjnoz, J. M., Taquini, A. C.: Renal hypertension. Springfield/Illinois: Charles C. Thomas 1946.Google Scholar
  5. Brown, J. J., Davies, D. L., Lever, A. F., Robertson, J. I. S.: Variations in plasma renin concentration in several physiological and pathological states. Canad. med. Ass. J. 90, 201 (1964).PubMedGoogle Scholar
  6. Btjmptjs, F. M., Schwarz, H., Page, I. H.: Synthesis and pharmacology of the octapeptide angiotonin. Science 125, 886 (1957).CrossRefGoogle Scholar
  7. Carretero, O. A., Bujak, B., Houle, J. A.: Renin isozymes of extrarenal origin. Amer. J. Physiol. 220, 1468 (1971).PubMedGoogle Scholar
  8. Collins, D. A., Harakal, C. D.: Changes in hypertensinase and hypertensinogen following nephrectomy. Circulât. Res. 2, 196 (1954).PubMedGoogle Scholar
  9. Dahlheim, H., Granger, P., Thurau, K.: A sensitive method for determination of renin activity in the single juxtaglomerular apparatus of the rat kidney. Pflügers Arch. ges. Physiol. 321, 303 (1970).CrossRefGoogle Scholar
  10. Dengler, H.: Über einen reninartigen Wirkstoff in Arterienextrakten. Naunyn-Schmiede-bergs Arch. exp. Path. Pharmak. 227, 481 (1956).CrossRefGoogle Scholar
  11. Deodhar, S. D., Cuppage, F. E., Gableman, E.: Studies on the mechanism of experimental proteinuria induced by renin. J. exp. Med. 120, 677 (1964).PubMedCrossRefGoogle Scholar
  12. Dexter, L., Haynes, F. W., Bridges, W. C.: The renal humoral pressor mechanism in man. I. Preparation and assay of human renin, human hypertensinogen, and hypertensin. J. clin. Invest. 24, 62 (1945).PubMedCrossRefGoogle Scholar
  13. Elltott, D. F., Peart, W. S.: The amino acid sequence in a hypertensin. Biochem. J. 65, 246 (1957).Google Scholar
  14. Fasciolo, J. C., Houssay, B. A., Taquini, A. C.: The blood-pressure raising secretion of the ischaemic kidney. J. Physiol. (Lond.) 94, 281 (1938).Google Scholar
  15. Ferris, T. F., Görden, P., Mulrow, P. J.: Rabbit uterus as a source of renin. Amer. J. Physiol. 212, 698 (1967).PubMedGoogle Scholar
  16. Finkielman, S., Nahmod, V. E.: In vitro production of angiotensin I by renal glomeruli. Nature (Lond.) 222, 186 (1969).CrossRefGoogle Scholar
  17. Fischer-Ferraro, C., Nahmod, V. E., Goldstein, D. J., Finkielman, S.: Angiotensin and renin in rat and dog brain. J. exp. Med. 133, 353 (1971).PubMedCrossRefGoogle Scholar
  18. Ganten, D., Hayduk, K., Brecht, H. M., Boucher, R., Genest, J.: Evidence of renin release or production in splanchnic territory. Nature (Lond.) 226, 551 (1970).CrossRefGoogle Scholar
  19. Ganten, D., Minnich, J. L., Granger, P., Hayduk, K., Brecht, H. M., Barbeau, A., Boucher, R., Genest, J.: Angiotensin-forming enzyme in brain tissue. Science 173, 64 (1972).CrossRefGoogle Scholar
  20. Ganten, D., Granger, P., Ganten, U., Boucher, R., Genest, J.: An intrinsic renin-angiotensin system in the brain. In: Hypertension 1972. Berlin-Heidelberg-New York: Springer 1972.Google Scholar
  21. Goormagtigh, N.: La présence de cellules endocrines dans la paroi des artérioles du rein et leur comportement dans l’ischémie renale. C. R. Soc. Biol. (Paris) 132, 465 (1939).Google Scholar
  22. Gould, A. B., Skeggs, L. T., Jr., Kahn, J. R.: The presence of renin activity in blood vessel walls. J. exp. Med. 119, 389 (1964).PubMedCrossRefGoogle Scholar
  23. Gould, A. B., Skeggs, L. T., Kahn, J. R.: Measurement of renin and substrate concentrations in human serum. Lab. Invest. 15, 1802 (1966).PubMedGoogle Scholar
  24. Gould, A. B., Goodman, S. A.: The effect of hypoxia on the renin-angiotensinogen system. Lab. Invest. 22, 443 (1970).PubMedGoogle Scholar
  25. Gould, A. B., Green, D.: Kinetics of the human renin and human substrate reaction. Cardiovasc. Res. 5, 86 (1971).PubMedCrossRefGoogle Scholar
  26. Grollman, A., Krishnamurty, V. S. R.: A new pressor agent of renal origin: its differentiation from renin and angiotensin. Amer. J. Physiol. 221, 1499 (1971).PubMedGoogle Scholar
  27. Gross, F., Schaechtelin, G., Ziegler, M., Berger, M.: A renin-like substance in the placenta and uterus of the rabbit. Lancet 1964 I, 914.CrossRefGoogle Scholar
  28. Haas, E., Goldblatt, H.: Kinetic constants of the human renin and human angiotensinogen reaction. Circulat. Res. 20, 45 (1967).PubMedGoogle Scholar
  29. Haas, E., Goldblatt, H., Gipson, E. C.: Extraction, purification, and acetylation of human renin and the production of antirenin to human renin. Arch. Biochem. Biophys. 110, 534 (1965).PubMedCrossRefGoogle Scholar
  30. Haas, E., Lamfrom, H., Goldblatt, H.: (1) Isolation and purification of hog renin. Arch. Biochem. Biophys. 42, 368 (1953).PubMedCrossRefGoogle Scholar
  31. Haas, E., Lamfrom, H., Goldblatt, H. (2) Biochemical and physicochemical studies on renin. Arch. Biochem. Biophys. 44, 63 (1953).PubMedCrossRefGoogle Scholar
  32. Haas, E., Lamfrom, H., Goldblatt, H.: A simple method for the extraction and partial purification of renin. Arch. Biochem. Biophys. 48, 256 (1954).PubMedCrossRefGoogle Scholar
  33. Haynes, F. W., Forsham, P. H., Hume, D. M.: Effects of ACTH, cortisone, desoxycortico- sterone, and epinephrine on the plasma hypertensinogen, and renin concentration of dogs. Amer. J. Physiol. 172, 265 (1953).PubMedGoogle Scholar
  34. Helmer, O. M., Griffith, R. S.: The effect of the administration of estrogens on the renin- substrate (hypertensinogen) content of rat plasma. Endocrinology 51, 421 (1952).PubMedCrossRefGoogle Scholar
  35. Helmer, O. M., Judson, W. E.: The quantitative determination of renin in the plasma of patients with arterial hypertension. Circulation 27, 1050 (1963).PubMedGoogle Scholar
  36. Hiwada, K., Kokubu, T., Yamamura, Y.: Inhibitory effect of rabbit bile on renin angiotensinogen reaction system. Jap. Circulat. J. (En.) 33, 1231 (1969).CrossRefGoogle Scholar
  37. Horky, K, Rojo-Ortega, J. M., Rodriguez, J., Boucher, R., Genest, J.: Renin, renin substrate, and angiotensin I-converting enzyme in the lymph of rats. Amer. J. Physiol. 220, 307 (1971).PubMedGoogle Scholar
  38. Itskovitz, H. D., Odya, C.: Intrarenal formation of angiotensin I. Science 174, 58 (1971).PubMedCrossRefGoogle Scholar
  39. Iwai, J., Knudsen, K. D., Dahl, L. K.: Genetic influence on the renin angiotensin system. Evidence for a renin inhibitor in hypertension prone rats. J. exp. Med. 131, 543 (1970).PubMedCrossRefGoogle Scholar
  40. Kemp, E., Rubin, I.: Renin purification by DEAE cellulose chromatography. Scand. J. clin. Lab. Invest. 14, 207 (1962).PubMedCrossRefGoogle Scholar
  41. Kemp, E., Rubin, I.: Molecular weight of renin determined by Sephadex gel filtration. Acta chem. scand. 18, 2403 (1964).CrossRefGoogle Scholar
  42. Kokubu, T., Ueda, E., Fujimoto, S., Hiwada, K, Kato, A., Akutsu, H., Yamamura, Y.: Peptide inhibitors of the renin-angiotensin system. Nature (Lond.) 217, 456 (1968).CrossRefGoogle Scholar
  43. Lee, H.-J., Wilson, I. B.: On the structure of renin substrate. Biochim. biophys. Acta (Amst.) 248, 530 (1971).Google Scholar
  44. Lentz, K. E., Skeggs, L. T., Jr., Woods, K. R., Kahn, J. R., Shumway, N. P.: The amino acid composition of hypertensin II and its biochemical relationship to hypertensin I. J. exp. Med. 104, 183 (1956).PubMedCrossRefGoogle Scholar
  45. Levine, M., Dorer, F. E., Kahn, J. R., Lentz, K. E., Skeggs, L. T.: Chemical determination of hog kidney renin by an automated method. Analyt. Biochem. 34, 366 (1970).PubMedCrossRefGoogle Scholar
  46. Levine, M., Lentz, K. E., Skeggs, L. T., Kahn, J. R., Dorer, F. E.: Preparation of hog renin free of pseudorenin. In: Hypertension—1972. Berlin-Heidelberg-New York: Springer 1972.Google Scholar
  47. Lubash, G. D., Peart, W. S.: Purification of human renin. Biochim. biophys. Acta (Amst.) 122, 289 (1966).Google Scholar
  48. Lucas, C. P., Fukuchi, S., Conn, J. W., Berlinger, F. G., Waldhausl, W.-K, Cohen, E. L., Rovner, D. R.: Purification of human renin. J. Lab. clin. Med. 76, 689 (1970).PubMedGoogle Scholar
  49. Mater, G. D., Morgan, W. S.: Purification of hog renin by column chromatography. Biochim. biophys. Acta (Amst.) 128, 193 (1966).Google Scholar
  50. Michelakis, A. M., Mizukoshi, H.: Distribution and disappearance rate of renin in man and dog. J. clin. Endocr. 33, 27 (1971).PubMedCrossRefGoogle Scholar
  51. Montague, D.: Kinetics of renin-angiotensinogen reaction in plasma of normal and nephrec- tomized rats. Amer. J. Physiol. 215, 78 (1968).PubMedGoogle Scholar
  52. Montague, D., Riniker, B., Brunner, H., Gross, F.: Synthesis and biological activities of a tetradecapeptide renin substrate. Amer. J. Physiol. 210, 591 (1966).PubMedGoogle Scholar
  53. Nairn, R. C., Chad wick, C. S., Fraser, K. B.: Purification of renin by electrophoresis, adsorption and immunological methods. Brit. J. exp. Path. 41, 214 (1960).PubMedGoogle Scholar
  54. Nasjletti, A., Masson, G. M. C.: Studies on renin substrate formation in a liver perfusion system. Circulât. Res. (1972) in press.Google Scholar
  55. Newsome, H. H.: Purification of bovine renin. Biochim. biophys. Acta (Amst.) 185, 247 (1969)Google Scholar
  56. Nustad, K., Rubin, I.: Subcellular localization of renin and kininogenase in the rat kidney. Brit. J. Pharmacol. 40, 326 (1970).Google Scholar
  57. Ogino, K., Matsunaga, M., Saito, N., Kir a, J., Takayasu, M.: Renin and acid adenosine triphosphatase as lysosomal enzymes. Jap. Circulât. J. (En.) 31, 1 (1967).CrossRefGoogle Scholar
  58. Page, I. H., Mubbin, J. W.: Renal hypertension. Chicago: Year Book Medical Publishers 1968.Google Scholar
  59. Page, I. H., Mwain, B., Knapp, G. M., Andrus, W. D.: The origin of renin-activator. Amer. J. Physiol. 135, 214 (1941).Google Scholar
  60. Passananti, G. T.: The purification of renin by use of ion-exchange chromatography. Biochim. biophys. Acta (Amst.) 34, 246 (1959).Google Scholar
  61. Peart, W. S., Lloyd, A. M., Thatcher, G. N., Lever, A. F., Payne, N., Stone, N.: Purification of pig renin. Biochem. J. 99, 708 (1966).PubMedGoogle Scholar
  62. Peters-Haefeli, L.: Rate of inactivation of endogenous or exogenous renin in normal and in renin-depleted rats. Amer. J. Physiol. 221, 1339 (1971).PubMedGoogle Scholar
  63. Plentl, A. A., Page, I. H., Davis, W. W.: The nature of renin activator. J. biol. Chem. 147, 143 (1943).Google Scholar
  64. Poulsen, K.: No evidence of active renin-inhibitors in plasma. The kinetics of the reaction between renin and substrate in non-pretreated plasma. Scand. J. clin. Lab. Invest. 27, 37 (1971).PubMedCrossRefGoogle Scholar
  65. Rakhit, S.: On the structure of the renin inhibitor from hog kidney. Canad. J. Biochem. 49, 1012 (1971).CrossRefGoogle Scholar
  66. Regoli, D.: Renin inactivation by human plasma. Canad. J. Physiol. Pharmacol. 48, 350 (1970).CrossRefGoogle Scholar
  67. Regoli, D., Brunner, H., Gross, F.: Untersuchungen über den Mechanismus der Wirkungsverstärkung von Renin nach Nephrektomie. Helv. physiol. pharmacol. Acta 19, C101 (1961).Google Scholar
  68. Reinharz, A., Roth, M.: Studies on renin with synthetic substrates. Europ. J. Biochem. 7, 334 (1969).PubMedCrossRefGoogle Scholar
  69. Reinharz, A., Roth, M., Haefeli, L., Schaechtelin, G.: Effect of some chemical agents on renin activity in vitro. Enzyme 12, 212 (1971).PubMedGoogle Scholar
  70. Rosenthal, J., Wolff, H. P., Weber, P., Dahlheim, H.: Enzyme kinetic studies on human renin and its purified homologous substrate. Amer. J. Physiol. 221, 1292 (1971).PubMedGoogle Scholar
  71. Rubin, I.: Purification of hog renin. Properties of purified hog renin. Scand. J. clin. Lab. Invest. 29, 51 (1972).PubMedCrossRefGoogle Scholar
  72. Ryan, J. W., Johnson, D. C.: The renin-like enzyme of rabbit uterus. Biochim. biophys. Acta (Amst.) 191, 386 (1969).Google Scholar
  73. Schaechtelin, G., Baechtold, N., Haefeli, L., Regoli, D., Gaudry-Paredes, A., Peters, G.: A renin-inactivating system in rat plasma. Amer. J. Physiol. 215, 632 (1968).PubMedGoogle Scholar
  74. Schweikert, J. R., Carey, R. M., Liddle, G. W., Island, D. W.: Characterization of the renal pressor substance of Grollman as angiotensin I. Circulât. Res. (1972) in press.Google Scholar
  75. Sealey, J. E., Gerten, J. N., Ledingham, J. G. G., Laragh, J. H.: Inhibition of renin by heparin. J. clin. Endoer. 27, 699 (1967).CrossRefGoogle Scholar
  76. Seki, T., Jenssen, T. A., Levin, Y., Erdos, E. G.: Active waterinsoluble derivative of renin. Nature (Lond.) 225, 864 (1970).CrossRefGoogle Scholar
  77. Sen, S., Hirasawa, K., Smeby, R. R., Bumpus, F. M.: Measurement of plasma renin substrate using homologous and heterologous renin. Amer. J. Physiol. 221, 1476 (1971).PubMedGoogle Scholar
  78. Sen, S., Smeby, R. R., Bumpus, F. M.: Antihypertensive effect of an isolated phospholipid. Amer. J. Physiol. 214, 337 (1968).PubMedGoogle Scholar
  79. 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
  80. Skeggs, L. T., Jr., Kahn, J. R., Shumway, N. P.: The isolation and assay of hypertensin from blood. J. exp. Med. 95, 241 (1952).PubMedCrossRefGoogle Scholar
  81. Skeggs, L. T., Jr., Lentz, K. E., Hochstrasser, H., Kahn, J. R.: The purification and partial characterization of several forms of hog renin substrate. J. exp. Med. 118, 73 (1963).PubMedCrossRefGoogle Scholar
  82. Skeggs, L. T., Lentz, K. E., Kahn, J. R., Dorer, F. E., Levine, M.: Pseudorenin. A new angiotensin-forming enzyme. Circulât. Res. 25, 451 (1969).PubMedGoogle Scholar
  83. Skeggs, L. T., Lentz, K. E., Kahn, J. R., Hochstrasser, H.: Studies on the preparation and properties of renin. Circulât. Res. 20–21 (Suppl. II), 91 (1967).Google Scholar
  84. 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
  85. Skeggs, L. T., Lentz, K. E., Kahn, J. R., Levine, M., Dorer, F. E.: Multiple forms of human kidney renin. In: Hypertension 1972. Berlin-Heidelberg-New York: Springer 1972.Google Scholar
  86. Skeggs, L. T., Jr., Lentz, K. E., Kahn, J. R., Shumway, N. P., Woods, K. R.: The amino acid sequence of hypertensin II. J. exp. Med. 104, 193 (1956).PubMedCrossRefGoogle Scholar
  87. Skeggs, L. T., Jr., Lentz, K. E., Kahn, J. R., Shtjmway, N. P.: The synthesis of a tetra- decapeptide renin substrate. J. exp. Med. 108, 283 (1958).PubMedCrossRefGoogle Scholar
  88. Smeby, R. R., Sen, S., Bumpus, F. M.: A naturally occurring renin inhibitor. Circulât. Res 20–21 (Suppl. II), 129 (1967).Google Scholar
  89. Tateishi, H., Nasjletti, A., Masson, G. M. C.: Role of renin in the regulation of angio- tensinogen levels in plasma. Proc. Soc. exp. Biol. (N. Y.) 137, 1424 (1971).Google Scholar
  90. Taylor, J., Cohen, S., Michelakis, A., Murakami, K., Inagami, T.: Isolation and characterization of a renin-like enzyme from mouse submaxillary glands. Fed. Proc. 30, 1146 (1971).Google Scholar
  91. Turrian, H.: Quelques caractéristiques du principe hypertensif contenu dans les glandes salivaires de la souris. Helv. physiol. pharmacol. Acta 18, 259 (1960).PubMedGoogle Scholar
  92. Waldhausl, W. K., Lucas, C. P., Conn, J. W., Lutz, J. H., Cohen, E. L.: Studies on the partial isolation of human renin. Biochim. biophys. Acta (Amst.) 221, 536 (1970).Google Scholar
  93. Werle, E., Trautschold, I., Krammer, K., Schmal, A.: Anreicherung und Immunspezifität des Isorenins der Glandula submaxillaris der Maus. Hoppe-Seylers Z. physiol. Chem. 349, 1441 (1968).CrossRefGoogle Scholar
  94. Werle, E., Yogel, R., Goldel, L. F.: Über ein blutdrucksteigerndes Prinzip in Extrakten aus der Glandula submaxillaris der weißen Maus. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 280, 236 (1957).Google Scholar
  95. Willard, R. F., Wilkinson, J. S., Turner, M. D., Glasgow, J. L., Bonar, J. R.: Studies on renin: purification and characterization. Fed. Proc. 29, 941 (1970).Google Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1974

Authors and Affiliations

  • Leonard T. Skeggs
  • Frederic E. Dorer
  • Joseph R. Kahn
  • Kenneth E. Lentz
  • Melvin Levine

There are no affiliations available

Personalised recommendations