Renin-Aldosterone System

  • James S. Milledge
Part of the Clinical Physiology book series (CLINPHY)


the effect of altitude and hypoxia on the renin-angiotensin-aldosterone system is interesting for many reasons. As a physician and mountaineer I have been puzzled for many years by the etiology of acute mountain sickness, especially high-altitude pulmonary edema (HAPE). A derangement of fluid homeostasis produced indirectly by hypoxia appeared to be one characteristic. The time lag of 6–24 h between exposure to hypoxia and the onset of symptoms suggests that hypoxia may stimulate a hormonal response which over this time course could upset fluid homeostasis enough to cause symptoms. For a time we considered the antidiuretic hormone, but, although levels are raised in cases of HAPE (4), this is more likely a result than a cause of the condition. Case reports of HAPE persistently stress the importance of strenuous exertion in the formation of this condition. We therefore decided to first study the effect of exercise typical of mountaineers on fluid balance.


Plasma Renin Activity Acute Mountain Sickness Aldosterone System Plasma Aldosterone Concentration Fluid Homeostasis 
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  1. 1.
    FRAYSER, R, I. D. RENNIE, G. W. GRAY, AND C. S. HOUSTON. Hormonal and electrolyte response to exposure to 17,500 ft. J. Appt. Physiol. 38: 636–642, 1975.Google Scholar
  2. 2.
    FRIEDLAND, J., AND E. SILVERSTEIN. A sensitive fluorimetric assay for serum angtiotensin-converting enzyme. Am. J. Clin. Pathol. 66: 416–424, 1976.PubMedGoogle Scholar
  3. 3.
    GAVIN, J. R, J. R. ROTH, D. M. NEVILLE, P. DE MEYTS, AND D. N. BUELL. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc. Natl. Acad. Sci. USA 71: 84–88, 1974.PubMedCrossRefGoogle Scholar
  4. 4.
    HACKET, P. H., M. L. FORSLING, J. S. MIL-LEDGE, AND D. RENNIE. Release of vasopressin in man at altitude. Harm. Metab. Res. 10: 571, 1978.CrossRefGoogle Scholar
  5. 5.
    HOGAN, R. P. III, T. A. KOTCHEN, A. E. BOYD III, AND L. H. HARTLEY. Effect of altitude on reninaldosterone system and metabolism of water and electrolytes. J. Appl. Physiol. 35: 385–390, 1973.PubMedGoogle Scholar
  6. 6.
    JANOSKI, A. H., B. K. WHITTEN, J. L. SHIELDS, AND J. P. HANNON. Electrolyte patternsand regulation in man during acute exposure to high altitude. Federation Proc. 28: 1185–1189, 1969.Google Scholar
  7. 7.
    KEYNES, R. J., G. W. SMITH, J. D. H. SLATER, M. M. BROWN, S. E. BROWN, N. N. PAYNE, T. P. JOWETT, AND C. C. MONGE. Renin and aldosterone at high altitude in man. J. Endocrinol. 92: 131–140, 1982.PubMedCrossRefGoogle Scholar
  8. 8.
    LEUENBERGER, P. J., S. A. STALCUP, R. B. MEL- LINS, L. M. GREENBAUM, AND G. M. TURINO. Decrease in angiotensin I conversion by acute hypoxia in dogs. Proc. Soc. Exp. Biot Med 158: 586–589, 1978.Google Scholar
  9. 9.
    MAHER, J. T., J. C. DENNISTON, D. L. WOLFE, AND A. CYMERMAN. Mechanism of the attenuated cardiac response to ß-adrenergic stimulation in chronic hypoxia. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 647–651, 1978.Google Scholar
  10. 10.
    MAHER, J. T., L. G. JONES, L. H. HARTLEY, G. H. WILLIAMS, AND L. I. ROSE. Aldosterone dynamics during graded exercise at sea level and high altitude. J. Appl. Physiol. 39: 18–22, 1975.PubMedGoogle Scholar
  11. 11.
    MILLEDGE, J. S., E. I. BRYSON, D. M. CATLEY, R. HESP, N. LUFF., B. D. MINTY, M. W. J. OLDER, N. N. PAYNE, M. P. WARD, AND W. R. WITHEY. Sodium balance, fluid homeostasis and the renin-aldosterone system during the prolonged exercise of hill walking. Clin. Sci. 62: 595–604, 1982.PubMedGoogle Scholar
  12. 12.
    MILLEDGE, J. S., AND D. M. CATLEY. Renin, aldosterone, and converting enzyme during exercise and acute hypoxia in humans. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 320–323, 1982.Google Scholar
  13. 13.
    MILLEDGE, J. S., D. M. CATLEY, F. D. BLUME, AND J. B. WEST. Renin, angiotensin-converting enzyme, and aldosterone in humans on Mount Everest. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55: 1109–1112, 1983.Google Scholar
  14. 14.
    MILLEDGE, J. S., D. M. CATLEY, M. P. WARD, E. S. WILLIAMS, AND C. R. A. CLARKE. Reninaldosterone and angiotensin-converting enzyme during prolonged altitude exposure. J. Appt. Physiol.: Respirat. Environ. Exercise Physiol. 55: 699–702, 1983.Google Scholar
  15. 15.
    MILLEDGE, J. S., D. M. CATLEY, E. S. WILLIAMS, W. R. WITHEY, AND B. D. MINTY. The effect of prolonged exercise at altitude on the renin aldosterone system. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55: 413–418, 1983.Google Scholar
  16. 16.
    MOLTENI, A., R. M. ZAKHEIM, K. B. MALLIS, AND L. MATTIOLI. The effect of chronic alveolar hypoxia in lung and serum angiotensin I converting enzyme activity. Proc. Soc. Exp. Biol. Med. 147: 263–265, 1974.PubMedGoogle Scholar
  17. 17.
    PINES, A., J. D. H. SLATER, AND T. P. JOWETT. The kidney and aldosterone in acclimatization at altitude. Br. J. Dis. Chest 71: 203–297, 1977.PubMedCrossRefGoogle Scholar
  18. 18.
    RYAN, J. W., AND U. S. RYAN. Pulmonary endothelial cells. Federation Proc. 36: 2683–2691, 1977.Google Scholar
  19. 19.
    SLATER, J. D. H., R. E. TUFFLEY, E. S. WILLIAMS, C. H. BERESFORD, P. H. SÖNKSEN, R. H. T. EDWARDS, R. P. EKINS, AND M. McLAUGHLIN. Control of aldosterone secretion during cclimatization to hypoxia in man. Clin. Sci. 37: 327–341, 1969.PubMedGoogle Scholar
  20. 20.
    STALCUP, S. A., J. S. LIPSET, J. M. WOUN, P. LEUENBERGER, AND R. B. MELLINS. Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia. J. Clin. Invest. 63: 966–976, 1979.PubMedCrossRefGoogle Scholar
  21. 21.
    SUTTON, J. R., G. W. VIOL, G. W. GRAY, M. M.FADDEN, AND P. M. KEANE. Renin, aldosterone, electrolyte, and cortisol responses to hypoxic decompres-sion. J. Appt Physiol.: Respirat. Environ. Exercise Physiol. 43: 421–424, 1977.Google Scholar
  22. 22.
    TUFFLEY, R. E., D. RUBENSTEIN, J. D. H. SLATER, AND E. S. WILLIAMS. Serum renin activity during exposure to hypoxia. J. Endocrinol. 48: 497–510, 1970.PubMedCrossRefGoogle Scholar
  23. 23.
    VOELKEL, N. F., L. HEGSTRAND, J. T. REEVES, I. F. McMURTY, AND P. B. MOLINOFF. Effects of hypoxia on density of ß-adrenergic receptors. J. Appt. Physiol.: Respirat. Environ. Exercise Physiol. 50: 363–366, 1981.Google Scholar
  24. 24.
    WILLIAMS, E. S. Salivary electrolyte composition at high altitude. Clin. Sci. 21: 37–42, 1961.PubMedGoogle Scholar
  25. 25.
    WILLIAMS, E. S. Electrolyte regulation during the adaptation of humans to life at high altitude. Proc. R. Soc. London Ser. B 165: 266–280, 1966.CrossRefGoogle Scholar
  26. 26.
    WILLIAMS, E. S., M. P. WARD, J. S. MILLEDGE, W. R. WITHEY, M. W. J. OLDER, AND M. L. FORSLING. Effect of the exercise of seven consecutive days hill-walking on fluid homeostatis. Clin. Sci. 56: 305316, 1979.Google Scholar
  27. 27.
    WITHEY, W. R., J. S. MILLEDGE, E. S. WILLIAMS, B. D. MINTY, E. I. BRYSON, N. P. LUFF, M. W. J. OLDER, AND J. M. BEELEY. Fluid and electrolyte homeostasis during prolonged exercise at alti- tude. J. Appt Physiol.: Respirat. Environ. Exercise Physiol. 55: 2–417, 1983.Google Scholar

Copyright information

© American Physiological Society 1984

Authors and Affiliations

  • James S. Milledge
    • 1
  1. 1.Medical Research Council Clinical Research CentreNorthwick Park HospitalHarrowEngland

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