Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Jun;51(6):1405–1412. doi: 10.1172/JCI106936

Renal handling of sodium and water in the hypothyroid rat

Clearance and micropuncture studies

Ulrich F Michael 1,2, Robert L Barenberg 1,2, Rafaelita Chavez 1,2, Carlos A Vaamonde 1,2, Solomon Papper 1,2
PMCID: PMC292277  PMID: 5024038

Abstract

Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals.

Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P]IN) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats.

These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agus Z. S., Puschett J. B., Senesky D., Goldberg M. Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog. J Clin Invest. 1971 Mar;50(3):617–626. doi: 10.1172/JCI106532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bank N., Mutz B. F., Aynedjian H. S. The role of "leakage" of tubular fluid in anuria due to mercury poisoning. J Clin Invest. 1967 May;46(5):695–704. doi: 10.1172/JCI105570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bijvoet O. L., van der Sluys Veer J., de Vries H. R., van Koppen A. T. Natriuretic effect of calcitonin in man. N Engl J Med. 1971 Apr 1;284(13):681–688. doi: 10.1056/NEJM197104012841301. [DOI] [PubMed] [Google Scholar]
  4. Brenner B. M., Bennett C. M., Berliner R. W. The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest. 1968 Jun;47(6):1358–1374. doi: 10.1172/JCI105828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brenner B. M., Galla J. H. Influence of postglomerular hematocrit and protein concentration on rat nephron fluid transfer. Am J Physiol. 1971 Jan;220(1):148–161. doi: 10.1152/ajplegacy.1971.220.1.148. [DOI] [PubMed] [Google Scholar]
  6. Burke T. J., Robinson R. R., Clapp J. R. Effect of arterial hematocrit on sodium reabsorption by the proximal tubule. Am J Physiol. 1971 May;220(5):1536–1541. doi: 10.1152/ajplegacy.1971.220.5.1536. [DOI] [PubMed] [Google Scholar]
  7. DEETJEN P., KRAMER K. [The relation of O2 consumption by the kidney to Na re-resorption]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1961;273:636–650. [PubMed] [Google Scholar]
  8. Demanet J. C. Effet de l'hypothyroïdie et de la régénération surrénalienne sur l'élimination urinaire d'une surcharge d'eau et de sodium chez le rat. Rev Fr Etud Clin Biol. 1965 Oct;10(8):842–844. [PubMed] [Google Scholar]
  9. DiScala V. A., Salomon M., Grishman E., Churg J. Renal structure in myxedema. Arch Pathol. 1967 Nov;84(5):474–485. [PubMed] [Google Scholar]
  10. FREGLY M. J., BRIMHALL R. L., GALINDO O. J. Effect of the antithyroid drug propylthiouracil on the sodium balance of rats. Endocrinology. 1962 Nov;71:693–700. doi: 10.1210/endo-71-5-693. [DOI] [PubMed] [Google Scholar]
  11. FREGLY M. J. Increased water exchange in rats treated with antithyroid drugs. J Pharmacol Exp Ther. 1961 Oct;134:69–76. [PubMed] [Google Scholar]
  12. Fregly M. J., Cade J. R., Waters I. W., Straw J. A., Taylor R. E., Jr Secretion of aldosterone by adrenal glands of propylthiouracil-treated rats. Endocrinology. 1965 Nov;77(5):777–784. doi: 10.1210/endo-77-5-777. [DOI] [PubMed] [Google Scholar]
  13. GOLDBERG R. C., CHAIKOFF I. L. Histopathological changes induced in the normal thyroid and other tissues of the rat by internal radiation with various doses of radioactive iodine. Endocrinology. 1950 Jan;46(1):72–90. doi: 10.1210/endo-46-1-72. [DOI] [PubMed] [Google Scholar]
  14. Gertz K. H., Mangos J. A., Braun G., Pagel H. D. On the glomerular tubular balance in the rat kidney. Pflugers Arch Gesamte Physiol Menschen Tiere. 1965 Sep 15;285(4):360–372. doi: 10.1007/BF00363236. [DOI] [PubMed] [Google Scholar]
  15. Gottschalk C. W., Leyssac P. P. Proximal tubular function in rats with low inulin clearance. Acta Physiol Scand. 1968 Nov;74(3):453–464. doi: 10.1111/j.1748-1716.1968.tb04253.x. [DOI] [PubMed] [Google Scholar]
  16. Hayslett J. P., Kashgarian M., Epstein F. H. Mechanism of change in the excretion of sodium per nephron when renal mass is reduced. J Clin Invest. 1969 Jun;48(6):1002–1006. doi: 10.1172/JCI106056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holmes E. W., Jr, DiScala V. A. Oxygen consumption, glycolysis, and sodium reabsorption in the hypothyroid rat kidney. Am J Physiol. 1971 Sep;221(3):839–843. doi: 10.1152/ajplegacy.1971.221.3.839. [DOI] [PubMed] [Google Scholar]
  18. Holmes E. W., Jr, DiScala V. A. Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat. J Clin Invest. 1970 Jun;49(6):1224–1236. doi: 10.1172/JCI106336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ismail-Beigi F., Edelman I. S. The mechanism of the calorigenic action of thyroid hormone. Stimulation of Na plus + K plus-activated adenosinetriphosphatase activity. J Gen Physiol. 1971 Jun;57(6):710–722. doi: 10.1085/jgp.57.6.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Izmail-Beigi F., Edelman I. S. Mechanism of thyroid calorigenesis: role of active sodium transport. Proc Natl Acad Sci U S A. 1970 Oct;67(2):1071–1078. doi: 10.1073/pnas.67.2.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Knox F. G., Howards S. S., Wright F. S., Davis B. B., Berliner R. W. Effect of dilution and expansion of blood volume on proximal sodium reabsorption. Am J Physiol. 1968 Nov;215(5):1041–1048. doi: 10.1152/ajplegacy.1968.215.5.1041. [DOI] [PubMed] [Google Scholar]
  22. Koch K. M., Aynedjian H. S., Bank N. Effect of acute hypertension on sodium reabsorption by the proximal tubule. J Clin Invest. 1968 Jul;47(7):1696–1709. doi: 10.1172/JCI105860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Landwehr D. M., Schnermann J., Klose R. M., Giebisch G. Effect of reduction in filtration rate on renal tubular sodium and water reabsorption. Am J Physiol. 1968 Sep;215(3):687–695. doi: 10.1152/ajplegacy.1968.215.3.687. [DOI] [PubMed] [Google Scholar]
  24. Milhaud G., Moukhtar M. S., Bourichon J., Perault A. M. Existence et activité de la thyrocalcitonine chez l'homme. C R Acad Sci Hebd Seances Acad Sci D. 1965 Nov 22;261(21):4513–4516. [PubMed] [Google Scholar]
  25. OSORIO J. A., ZADUNAISKY J. A. Clearances de inulina y diodrast y peso renal en ratas tratadas con I131 y polvo de tiroides. Rev Soc Argent Biol. 1956 Sep-Nov;32(6-8):195–203. [PubMed] [Google Scholar]
  26. Rodicio J., Herrera-Acosta J., Sellman J. C., Rector F. C., Jr, Seldin D. W. Studies on glomerulotubular balance during aortic constriction, ureteral obstruction and venous occlusion in hydropenic and saline-loaded rats. Nephron. 1969;6(3):437–456. doi: 10.1159/000179744. [DOI] [PubMed] [Google Scholar]
  27. STEPHAN F., JAHN H., METZ B. Action de l'insuffisance thyroidienne sur l'elimination urinaire de l'eau, du sodium et du potassium chez le rat surrénalectomisé. C R Seances Soc Biol Fil. 1959;153(3):463–467. [PubMed] [Google Scholar]
  28. STEPHAN F., JAHN H., REVILLE P. ETUDE COMPARATIVE DE LA CONCENTRATION, DE LA COMPOSITION ET DU D'EBIT DES URINES DU RAT NORMAL ET DU RAT HYPOTHYROUIDIEN SOUMIS 'A DES 'EPREUVES AIGUUES DE SURCHARGE ISOTONIQUE. J Physiol (Paris) 1964 Mar-Apr;56:233–258. [PubMed] [Google Scholar]
  29. STEPHAN F., JAHN H., REVILLE P., URBAN M. ACTION DE L'INSUFFISANCE THYROUIDIENNE CHRONIQUE SUR LE D'EBIT URINAIRE ET LE POUVOIR DE CONCENTRATION DU REIN CHEZ LE RAT. Rev Fr Etud Clin Biol. 1963 Nov;8:890–902. [PubMed] [Google Scholar]
  30. Salako L. A., Smith A. J., Smith R. N. The effects of porcine calcitonin on renal function in the rabbit. J Endocrinol. 1971 Jul;50(3):485–491. doi: 10.1677/joe.0.0500485. [DOI] [PubMed] [Google Scholar]
  31. Schrier R. W., McDonald K. M., Wells R. E., Lauler D. P. Influence of hematocrit and colloid on whole blood viscosity during volume expansion. Am J Physiol. 1970 Feb;218(2):346–352. doi: 10.1152/ajplegacy.1970.218.2.346. [DOI] [PubMed] [Google Scholar]
  32. TAYLOR R. E., Jr, FREGLY M. J. RENAL RESPONSE OF PROPYLTHIOURACIL-TREATED RATS TO INJECTED MINERALOCORTICOIDS. Endocrinology. 1964 Jul;75:33–41. doi: 10.1210/endo-75-1-33. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES