Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The localization over time of exogenous aldosterone and angiotensin II in various organs


Central nervous system effects have been demonstrated for angiotensin II and suggested for aldosterone. In order to determine whether either of these chemicals naturally crosses the blood-brain barrier, radioactive aldosterone and angiotensin II were introduced via intracardiac injections in rats. Samples of blood, liver, kidney, adrenals, cerebral cortex, and hypothalamus were collected at three, 15, and 60 minutes, frozen, dissolved, and counted. Blood levels for aldosterone and angiotensin II remained constant over 60 minutes. Aldosterone accumulated in the liver, kidney, adrenals and hypothalamus three minutes after injection, and levels diminished over time. Angiotensin II levels peaked in the adrenal, kidney, and liver after three minutes, and in the hypothalamus after 15 minutes. Cerebral cortex levels were lower than hypothalamic levels by 30% for aldosterone and 50% for angiotensin II. This suggests that both drugs may enter the central nervous system and selectively accumulate in the hypothalamus.

This is a preview of subscription content, log in to check access.


  1. Abelson, D., Baron, D. N. and Toakley, J. G.: Studies of cerebrospinal fluid following oral administration of cortisone acetate or hydrocortisone. J. Endocrinol.12, 87–92, 1955.

  2. Bakay, L.:The Blood-Brain Barrier, with Special Regard to the Use of Radioactive Isotopes. Springfield, Charles C Thomas, 1956.

  3. Bakay, L.: Dynamic aspects of the blood-brain barrier.In Richter, D. (ed.),Metabolism of the Nervous System, New York, Pergamon Press, 1957.

  4. Bennett, J. P., Logan, W. J. and Snyder, S. H.: Amino acids as central nervous transmitters: The influence of ions, amino acid analogues, and ontogeny on transport systems for L-glutamic and L-aspartic acid and glycine into central nervous synaptosomes of the rat. J. Neurochem.21, 1533–1550, 1973.

  5. Barlow, D. F.: Clinical aspects of the blood-brain barrier. Ann. Rev. Med.15, 187–202, 1964.

  6. Brodie, B. R. and Hogbon, C. A.: Some physicochemical factors in drug action. J. Pharm. Pharmacol.9, 345–380, 1957.

  7. Brodie, B. R., Kurz, H. and Schenker, L. A.: The importance of dissociation constant and lipid solubility in influencing the passage of drugs into the cerebrospinal fluid. J. Pharmacol. Exp. Ther.130, 20–25, 1960.

  8. Broman, T.:The Permeability of the Cerebral Vessels in Normal and Pathological Conditions. Copenhagen, Munksgaard, 1949.

  9. Broman, T., Radner, S. and Svenberg, L.: Duration of experimental disturbances in cerebrovascular permeability due to circumscribed gross damage to the brain. Acta Psychia. Neurol.24, 167–173, 1949.

  10. Christy, N. P. and Fishman, R. A.: Studies of the blood-cerebrospinal fluid barrier to Cortisol in the dog. J. Clin. Invest.40, 1997–2006, 1961.

  11. Daughaday, W. H.: Binding of corticosteroids by plasma proteins. Arch. Intern. Med.101, 286–290, 1958.

  12. Daughaday, W. H. and Mariz, I. K.: The binding of steroid hormones by plasma proteins.In Pincus and Vollmer (eds.),Biological Activities of Steroids in Relation to Cancer, New York, Academic Press, 1960.

  13. Davson, H.: Intracranial and intraocular fluids.In Handbook of Physiology, American Physiology Society, Volume 3, 1960.

  14. Derymaekor, A. and Theowisson-Lesoisse: Permeability of cerebral blood vessels studied with radioactive iodinated albumin and Nal. Rev. Franc. Etud. Clin. Biol.8, 156–164, 1963.

  15. Edstrom, R. and Steinwall, O.: The blood-brain barrier phenomenon—the relative importance of permeability and cellular transport mechanisms. Acta Neurol. Scand.37, 1–21, 1961.

  16. Ehrlich, P.:Das Sauerstoff-Bedurfniss des Organismus, Line Farbonalalytische Studie. August Hirschwald Berlin, 1885.

  17. Fischer-Ferrara, C., Nahmod, V. E., Goldstein, D. J. and Finkielman, S.: Angiotensin and renin in rat and dog brain. J. Exper. Med.133, 353–361, 1971.

  18. Fishman, R. A. and Christy, N. P.: Fate of adrenal cortical steriods following: intrathocal injection. Neurology15, 1–6, 1965.

  19. Fleishhauer, K.: Untersuchungen am Ependym des Zwischenand Mittelhims der Landschildkrote. Z. Zellforsch.46, 729–767, 1957.

  20. Fleishhauer, K.: Uber die Feinstruktur der Faserglia. Z. Zellforsch.47, 548–556, 1958.

  21. Fleishhauer, K.: Fluorescenzmikroskopische Untersuchungen an der Faserglia. Z. Zellforsch.51, 467–496, 1960.

  22. Ford, D. H.: The relationship of the blood-brain barrier of the rat to131I-labelled triiodothyronine. J. Nerv. Ment. Dis.120, 530–541, 1959.

  23. Glauser, S., Wagner, H., Glauser, E. and Sevy, R.: A proposed structure and active site of angiotensin II. Currents in Modern Biol.3, 221–224, 1970.

  24. Goodfriend, T. L.: Receptors for angiotensin I and II. Circulation Res.27, Suppl. 1, 163, 1970.

  25. Gordon, M. W., Sims, J. A., Hanson, R. K. and Kuttner, R. E.: The effects of some psychopharmacological agents and other drugs on the uptake of an amino acid by brain. J. Neurochem.9, 477–486, 1962.

  26. Helton, E. D. and Holmes, W. N.: The distribution and metabolism of labelled corticosteroids in the duck. J. Endocrinol.56, 361–385, 1973.

  27. Hendler, N. and Blake, W. D.: Hypothalamic implants of angiotensin II, carbachol, and nor-epinephrine on water and NaCl solution intake in rats. Commun, in Behav. Biol.4, 41–48, 1969.

  28. Kandel, M. and Gornell, A. G.: Effect of glass surfaces on the liquid scintillation counting of aldosterone. Canad. J. Biochem.41, 1833–1837, 1964.

  29. Macklin, C. C. and Macklin, M. T.: A study of a brain repair in the rat by use of trypan blue. Arch. Neurol. Psychiat.3, 354–394, 1926.

  30. MacCurdy, J. T. and Evans, H. M.: Experimentelle Laisionen des Central-nervon systems, untersucht mit Hilfe der vitellen Farbung. Klin. Wochenschr.49, 1695–1696, 1912.

  31. Mayer, S., Maickel, R. P. and Brodie, B. B.: Kinetics of penetration of drugs and other foreign compounds into cerebrospinal fluid and brain. J. Pharmacol. Exp. Ther.127, 205–211, 1959.

  32. Peterson, N. A. and Chaikoff, I. L.: Uptake of intravenously injected 4-14C-cortisol by adult rat brain. J. Neurochem.10, 17–23, 1963.

  33. Ponten, U., Ratcheson, R. A. and Siesjo, B. K.: Metabolic changes in the brains of mice frozen in liquid nitrogen. J. Neurochem.21, 1121–1126, 1973.

  34. Rapoport, S. I., Hori, M. and Klatzo, I.: Testing of a hypothesis for osmotic opening of the blood-brain barrier. Am. J. Physiol.223, 323–331, 1972.

  35. Reed, D. J. and Woodbury, D. M.: Kinetics of movement of iodide, sucrose, insulin, and radio-iodinated serum albumin in the central nervous system and cerebrospinal fluid of the rat. J. Physiol.169, 816–850, 1963.

  36. Rioux, F., Park, W. K. and Regoli, D.: Application of drug-receptor theories to angiotensin. Can. J. Physiol. Pharmacol.51, 665–672, 1973.

  37. Ruf, K. and Steiner, F. A.: Steroid sensitive single neurons in rat hypothalamus and midbrain: identification by microelectrophoresis. Science156, 667–669, 1967.

  38. Schaltenbrand, G. and Bailey, T. P.: Die perivaskular Piagliamembran des Gehirns. J. Psychol. Neurol.35, 199–278, 1928.

  39. Schmiedek, P., Badee, W. and Baethmann, R.: Cerebral uptake of a 3H-labelled spirolactone compound in the dog. Eur. J. Pharmacol.21, 238–241, 1973.

  40. Slaunwhite, W. R. and Sandberg, A. A.: Transcortin: a corticosteroid binding protein of plasma. J. Clin. Invest.38, 384, 1959.

  41. Steinwall, P.: Transport mechanisms in certain bloodbrain barrier phenomena—a hypothesis. Acta Psychiat. Scand. [Suppl.]1950, 314–318, 1961.

  42. Swaneck, G.: Stereospecific nuclear and cytosol aldosterone-binding proteins for various tissues. Nephron6, 297–302, 1969.

  43. Swanson, L. W., Marshal, G. R., Needleman, P. and Sharpe, L. G.: Characterization of central angiotensin II receptor involved in the elicitation of drinking in the rat. Brain Res.49, 441–446, 1973.

  44. Swanson, L. W. and Sharpe, L. G.: Centrally induced drinking: comparison of angiotensin II-and carbachol-sensitive sites in rats. Am. J. Physiol.225, 566–573, 1973.

  45. Tschirgi, R. D.: Blood-brain barrier: fact or fancy? Fed. Proc.21, 665–671, 1962.

  46. Weil-Melherbe, J., Axelrod, H. J. and Tomchick, R.: Blood-brain barrier for adrenaline. Science129, 1226–1227, 1959.

  47. Wilson, C. W. M. and Brodie, B. B.: The absence of blood-brain barrier from certain areas of the central nervous system. J. Pharmacol. Exp. Ther.133, 332–334, 1961.

Download references

Author information

Correspondence to Nelson H. Hendler.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hendler, N.H., Livingston, A. The localization over time of exogenous aldosterone and angiotensin II in various organs. Pav. J. Biol. Sci. 13, 187–193 (1978).

Download citation


  • Aldosterone
  • Central Nervous System Effect
  • Intracardiac Injection
  • Hypothalamic Level
  • Active Transport Process