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. 1990 Oct;86(4):1023–1029. doi: 10.1172/JCI114804

Hyponatremia in rats induces downregulation of vasopressin synthesis.

A G Robinson 1, M M Roberts 1, W A Evron 1, J G Verbalis 1, T G Sherman 1
PMCID: PMC296828  PMID: 2211999

Abstract

Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality.

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  1. AMATRUDA T. T., Jr, MULROW P. J., GALLAGHER J. C., SAWYER W. H. CARCINOMA OF THE LUNG WITH INAPPROPRIATE ANTIDIURESIS. DEMONSTRATION OF ANTIDIURETIC-HORMONE-LIKE ACTIVITY IN TUMOR EXTRACT. N Engl J Med. 1963 Sep 12;269:544–549. doi: 10.1056/NEJM196309122691102. [DOI] [PubMed] [Google Scholar]
  2. Anderson R. J., Chung H. M., Kluge R., Schrier R. W. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985 Feb;102(2):164–168. doi: 10.7326/0003-4819-102-2-164. [DOI] [PubMed] [Google Scholar]
  3. Balment R. J., Brimble M. J., Forsling M. L. Release of oxytocin induced by salt loading and its influence on renal excretion in the male rat. J Physiol. 1980 Nov;308:439–449. doi: 10.1113/jphysiol.1980.sp013481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bichet D. G., Van Putten V. J., Schrier R. W. Potential role of increased sympathetic activity in impaired sodium and water excretion in cirrhosis. N Engl J Med. 1982 Dec 16;307(25):1552–1557. doi: 10.1056/NEJM198212163072504. [DOI] [PubMed] [Google Scholar]
  5. Burbach J. P., Liu B., Voorhuis T. A., Van Tol H. H. Diurnal variation in vasopressin and oxytocin messenger RNAs in hypothalamic nuclei of the rat. Brain Res. 1988 Sep;464(2):157–160. doi: 10.1016/0169-328x(88)90007-1. [DOI] [PubMed] [Google Scholar]
  6. Carrazana E. J., Pasieka K. B., Majzoub J. A. The vasopressin mRNA poly(A) tract is unusually long and increases during stimulation of vasopressin gene expression in vivo. Mol Cell Biol. 1988 Jun;8(6):2267–2274. doi: 10.1128/mcb.8.6.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carter D. A., Murphy D. Diurnal rhythm of vasopressin mRNA species in the rat suprachiasmatic nucleus: independence of neuroendocrine modulation and maintenance in explant culture. Brain Res Mol Brain Res. 1989 Dec;6(4):233–239. doi: 10.1016/0169-328x(89)90069-7. [DOI] [PubMed] [Google Scholar]
  8. Flear C. T., Gill G. V., Burn J. Hyponatraemia: mechanisms and management. Lancet. 1981 Jul 4;2(8236):26–31. doi: 10.1016/s0140-6736(81)90261-0. [DOI] [PubMed] [Google Scholar]
  9. Gainer H., Sarne Y., Brownstein M. J. Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides. J Cell Biol. 1977 May;73(2):366–381. doi: 10.1083/jcb.73.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gross P. A., Anderson R. J. Effects of DDAVP and AVP on sodium and water balance in conscious rat. Am J Physiol. 1982 Nov;243(5):R512–R519. doi: 10.1152/ajpregu.1982.243.5.R512. [DOI] [PubMed] [Google Scholar]
  11. Gross P., Pehrisch H., Rascher W., Hackenthal E., Schömig A., Ritz E. Vasopressin in hyponatremia: what stimuli? J Cardiovasc Pharmacol. 1986;8 (Suppl 7):S92–S95. [PubMed] [Google Scholar]
  12. Herman J. P., Marciano F. F., Wiegand S. J., Gash D. M. Selective cell death of magnocellular vasopressin neurons in neurohypophysectomized rats following chronic administration of vasopressin. J Neurosci. 1987 Aug;7(8):2564–2575. [PMC free article] [PubMed] [Google Scholar]
  13. Jacobowitz D. M. Removal of discrete fresh regions of the rat brain. Brain Res. 1974 Nov 8;80(1):111–115. doi: 10.1016/0006-8993(74)90726-4. [DOI] [PubMed] [Google Scholar]
  14. Kleinfeld M., Casimir M., Borra S. Hyponatremia as observed in a chronic disease facility. J Am Geriatr Soc. 1979 Apr;27(4):156–161. doi: 10.1111/j.1532-5415.1979.tb06439.x. [DOI] [PubMed] [Google Scholar]
  15. LEAF A., BARTTER F. C., SANTOS R. F., WRONG O. Evidence in man that urinary electrolyte loss induced by pitressin is a function of water retention. J Clin Invest. 1953 Sep;32(9):868–878. doi: 10.1172/JCI102805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moses A. M. Is there an osmotic threshold for vasopressin release? Am J Physiol. 1978 Mar;234(3):E339–E340. doi: 10.1152/ajpendo.1978.234.3.E339. [DOI] [PubMed] [Google Scholar]
  17. Rehbein M., Hillers M., Mohr E., Ivell R., Morley S., Schmale H., Richter D. The neurohypophyseal hormones vasopressin and oxytocin. Precursor structure, synthesis and regulation. Biol Chem Hoppe Seyler. 1986 Aug;367(8):695–704. doi: 10.1515/bchm3.1986.367.2.695. [DOI] [PubMed] [Google Scholar]
  18. Robertson G. L. The regulation of vasopressin function in health and disease. Recent Prog Horm Res. 1976;33:333–385. doi: 10.1016/b978-0-12-571133-3.50015-5. [DOI] [PubMed] [Google Scholar]
  19. Robinson A. G. DDAVP in the treatment of central diabetes insipidus. N Engl J Med. 1976 Mar 4;294(10):507–511. doi: 10.1056/NEJM197603042941001. [DOI] [PubMed] [Google Scholar]
  20. Robinson A. G., Roberts M. M., Evron W. A., Janocko L. E., Hoffman G. E. Total translation of vasopressin and oxytocin in neurohypophysis of rats. Am J Physiol. 1989 Jul;257(1 Pt 2):R109–R117. doi: 10.1152/ajpregu.1989.257.1.R109. [DOI] [PubMed] [Google Scholar]
  21. Rodbard D., Munson P. J. Is there an osmotic threshold for vasopressin release? Am J Physiol. 1978 Mar;234(3):E340–E342. doi: 10.1152/ajpendo.1978.234.3.E340. [DOI] [PubMed] [Google Scholar]
  22. Schrier R. W., Berl T., Anderson R. J. Osmotic and nonosmotic control of vasopressin release. Am J Physiol. 1979 Apr;236(4):F321–F332. doi: 10.1152/ajprenal.1979.236.4.F321. [DOI] [PubMed] [Google Scholar]
  23. Schrier R. W., Bichet D. G. Osmotic and nonosmotic control of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders. J Lab Clin Med. 1981 Jul;98(1):1–15. [PubMed] [Google Scholar]
  24. Seif S. M., Huellmantel A. B., Platia M. P., Haluszczak C., Robinson A. G. Isolation, radioimmunoassay and physiologic secretion of rat neurophysins. Endocrinology. 1977 May;100(5):1317–1326. doi: 10.1210/endo-100-5-1317. [DOI] [PubMed] [Google Scholar]
  25. Seif S. M., Robinson A. G., Zenser T. V., Davis B. B., Huellmantel A. B., Haluszczak C. Neurohypophyseal peptides in hypothyroid rats: plasma levels and kidney response. Metabolism. 1979 Feb;28(2):137–143. doi: 10.1016/0026-0495(79)90078-7. [DOI] [PubMed] [Google Scholar]
  26. Sherman T. G., Watson S. J. Differential expression of vasopressin alleles in the Brattleboro heterozygote. J Neurosci. 1988 Oct;8(10):3797–3811. doi: 10.1523/JNEUROSCI.08-10-03797.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Uhl G. R., Reppert S. M. Suprachiasmatic nucleus vasopressin messenger RNA: circadian variation in normal and Brattleboro rats. Science. 1986 Apr 18;232(4748):390–393. doi: 10.1126/science.3961487. [DOI] [PubMed] [Google Scholar]
  28. Van Tol H. H., Kiss J. Z., Burbach J. P. Differential responses in vasopressin and oxytocin gene expression in distinct hypothalamic nuclei after hypothalamoneurohypophyseal disconnection and vasopressin substitution. Neuroendocrinology. 1989 Apr;49(4):337–343. doi: 10.1159/000125137. [DOI] [PubMed] [Google Scholar]
  29. Verbalis J. G. An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat. Am J Physiol. 1984 Oct;247(4 Pt 1):E540–E553. doi: 10.1152/ajpendo.1984.247.4.E540. [DOI] [PubMed] [Google Scholar]
  30. Verbalis J. G., Baldwin E. F., Robinson A. G. Osmotic regulation of plasma vasopressin and oxytocin after sustained hyponatremia. Am J Physiol. 1986 Mar;250(3 Pt 2):R444–R451. doi: 10.1152/ajpregu.1986.250.3.R444. [DOI] [PubMed] [Google Scholar]
  31. Verbalis J. G., Baldwin E. F., Robinson A. G. Osmotic regulation of plasma vasopressin and oxytocin after sustained hyponatremia. Am J Physiol. 1986 Mar;250(3 Pt 2):R444–R451. doi: 10.1152/ajpregu.1986.250.3.R444. [DOI] [PubMed] [Google Scholar]
  32. Verbalis J. G., Drutarosky M. D. Adaptation to chronic hypoosmolality in rats. Kidney Int. 1988 Sep;34(3):351–360. doi: 10.1038/ki.1988.188. [DOI] [PubMed] [Google Scholar]
  33. Verbalis J. G., Drutarosky M. D., Ertel R. J., Vollmer R. R. Adaptive responses to sustained volume expansion in hyponatraemic rats. J Endocrinol. 1989 Jul;122(1):421–431. doi: 10.1677/joe.0.1220421. [DOI] [PubMed] [Google Scholar]
  34. Weitzman R. E., Fisher D. A. Log linear relationship between plasma arginine vasopressin and plasma osmolality. Am J Physiol. 1977 Jul;233(1):E37–E40. doi: 10.1152/ajpendo.1977.233.1.E37. [DOI] [PubMed] [Google Scholar]
  35. Zimmerman E. A., Robinson A. G. Hypothalamic neurons secreting vasopressin and neurophysin. Kidney Int. 1976 Jul;10(1):12–24. doi: 10.1038/ki.1976.75. [DOI] [PubMed] [Google Scholar]
  36. Zingg H. H., Lefebvre D. L., Almazan G. Regulation of poly(A) tail size of vasopressin mRNA. J Biol Chem. 1988 Aug 15;263(23):11041–11043. [PubMed] [Google Scholar]
  37. Zingg H. H., Lefebvre D., Almazan G. Regulation of vasopressin gene expression in rat hypothalamic neurons. Response to osmotic stimulation. J Biol Chem. 1986 Oct 5;261(28):12956–12959. [PubMed] [Google Scholar]

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