Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Nov;58(5):1201–1208. doi: 10.1172/JCI108573

The critical role of the adrenal gland in the renal regulation of acid-base equilibrium during chronic hypotonic expansion. Evidence that chronic hyponatremia is a potent stimulus to aldosterone secretion.

J J Cohen, H N Hulter, N Smithline, J C Melby, W B Schwartz
PMCID: PMC333288  PMID: 993340

Abstract

Recent studies have shown that chronic hypotonic volume expansion (HVE) induced by administration of vasopressin and water stimulates distal hydrogen ion secretion and thereby (a) permits dogs with HCl-acidosis to restore acid-base equilibrium to normal despite continued acid feeding and (b) permits normal dogs to conserve filtered bicarbonate quantitatively despite the natriuresis induced by water retention. To examine whether these effects of chronic HVE are mediated by augmented mineralocorticoid secretion, urinary and plasma aldosterone levels were monitored during prolonged administration of vasopressin. In HCl-fed animals, the HVE-induced rise in plasma [HCO3] (from 13.8 to 21.3 meq/liter) was associated with a rise in aldosterone excretion from 0.45 to 0.88 mug/day (P less than 0.02). In normal animals, in which plasma [HCO3] remained stable during HVE (21.9 vs. 20.0 meq/liter), aldosterone excretion rose from 0.51 to 2.28 mug/day (P less than 0.02) and plasma aldosterone concentration rose from 8.1 to 39.8 ng/100 ml (P less than 0.01). Vasopressin and water were also administered to adrenalectomized animals maintained on glucocorticoids and a slightly subphysiologic replacement schedule of mineralocorticoids. In the HCl-fed adrenalectomized group, plasma [HCO3], instead of rising to normal, showed no significant change (16.9 vs. 15.0 meq/liter). In the non-HCl-fed adrenalectomized group, plasma [HCO3], rather than remaining stable, fell significantly (20.3 vs 16.5 meq/liter, P less than 0.1). Two conclusions can be drawn from this study: (a) the well-known inhibitory effect of volume expansion on aldosterone secretion can be overridden by a potent stimulatory effect on the adrenal produced by severe chronic hypotonicity, and (b) the response of plasma [HCO3] observed during severe chronic HVE is mediated by augmented mineralocorticoid secretion. These findings, furthermore, offer a possible explanation for the puzzling observation that plasma [HCO3] in patients with the syndrome of inappropriate antidiuretic hormone secretion is maintained at normal levels even in the face of severe hyponatremia.

Full text

PDF
1201

Selected References

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

  1. Arbus G. S., Herbert L. A., Levesque P. R., Etsten B. E., Schwartz W. B. Characterization and clinical application of the "significance band" for acute respiratory alkalosis. N Engl J Med. 1969 Jan 16;280(3):117–123. doi: 10.1056/NEJM196901162800301. [DOI] [PubMed] [Google Scholar]
  2. BARBER J. K., BARTTER F. C., DELEA C., DUNCAN L. E., Jr, LIDDLE G. W. The regulation of aldosterone secretion in man: the role of fluid volume. J Clin Invest. 1956 Nov;35(11):1306–1315. doi: 10.1172/JCI103386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BLAIR WEST J. R., COGHLAN J. P., DENTON D. A., GODING J. R., WINTOUR M., WRIGHT R. D. THE CONTROL OF ALDOSTERONE SECRETION. Recent Prog Horm Res. 1963;19:311–383. [PubMed] [Google Scholar]
  4. Bartter F. C., Schwartz W. B. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967 May;42(5):790–806. doi: 10.1016/0002-9343(67)90096-4. [DOI] [PubMed] [Google Scholar]
  5. DAVIS J. O., URQUHART J., HIGGINS J. T., Jr The effects of alteration of plasma sodium and potassium concentration on aldosterone secretion. J Clin Invest. 1963 May;42:597–609. doi: 10.1172/JCI104750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DENTON D. A., GODING J. R., WRIGHT R. D. Control of adrenal secretion of electrolyte-active steroids; adrenal stimulation by cross-circulation experiments in conscious sheep. Br Med J. 1959 Sep 26;2(5151):522–530. doi: 10.1136/bmj.2.5151.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. De Sousa R. C., Harrington J. T., Ricanati E. S., Shelkrot J. W., Schwartz W. B. Renal regulation of acid-base equilibrium during chronic administration of mineral acid. J Clin Invest. 1974 Feb;53(2):465–476. doi: 10.1172/JCI107580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fichman M. P., Bethune J. E. The role of adrenocorticoids in the inappropriate antidiuretic hormone syndrome. Ann Intern Med. 1968 Apr;68(4):806–820. doi: 10.7326/0003-4819-68-4-806. [DOI] [PubMed] [Google Scholar]
  9. Fichman M. P., Michelakis A. M., Horton R. Regulation of aldosterone in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). J Clin Endocrinol Metab. 1974 Jul;39(1):136–144. doi: 10.1210/jcem-39-1-136. [DOI] [PubMed] [Google Scholar]
  10. Heinemann H. O., Laragh J. H. Inappropriate renal sodium loss reverted by vena cava obstruction. Ann Intern Med. 1966 Oct;65(4):708–721. doi: 10.7326/0003-4819-65-4-708. [DOI] [PubMed] [Google Scholar]
  11. IVY H. K. Renal sodium loss and bronchogenic carcinoma. Associated autonomic neuropathy. Arch Intern Med. 1961 Jul;108:47–55. doi: 10.1001/archinte.1961.03620070049007. [DOI] [PubMed] [Google Scholar]
  12. KNOCHEL J. P., OSBORN J. R., COOPER E. B. EXCRETION OF ALDOSTERONE IN INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE FOLLOWING HEAD TRAUMA. Metabolism. 1965 Jun;14:715–725. doi: 10.1016/0026-0495(65)90055-7. [DOI] [PubMed] [Google Scholar]
  13. Lowance D. C., Garfinkel H. B., Mattern W. D., Schwartz W. B. The effect of chronic hypotonic volume expansion on the renal regulation of acid-base equilibrium. J Clin Invest. 1972 Nov;51(11):2928–2940. doi: 10.1172/JCI107117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mayes D., Furuyama S., Kem D. C., Nugent C. A. A radioimmunoassay for plasma aldosterone. J Clin Endocrinol Metab. 1970 May;30(5):682–685. doi: 10.1210/jcem-30-5-682. [DOI] [PubMed] [Google Scholar]
  15. McCaa R. E., McCaa C. S., Read D. G., Bower J. D., Guyton A. C. Increased plasma aldosterone concentration in response to hemodialysis in nephrectomized man. Circ Res. 1972 Oct;31(4):473–480. doi: 10.1161/01.res.31.4.473. [DOI] [PubMed] [Google Scholar]
  16. Nolph K. D., Schrier R. W. Sodium, potassium and water metabolism in the syndrome of inappropriate antidiuretic hormone secretion. Am J Med. 1970 Oct;49(4):534–545. doi: 10.1016/s0002-9343(70)80048-1. [DOI] [PubMed] [Google Scholar]
  17. POLAK A., HAYNIE G. D., HAYS R. M., SCHWARTZ W. B. Effects of chronic hypercapnia on electrolyte and acid-base equilibrium. I. Adaptation. J Clin Invest. 1961 Jul;40:1223–1237. doi: 10.1172/JCI104353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. St Cyr M. J., Sancho J. M., Melby J. C. Quantitation of plasma aldosterone by radioimmunoassay. Clin Chem. 1972 Nov;18(11):1395–1402. [PubMed] [Google Scholar]
  19. THORN N. A., TRANSBOL I. HYPONATREMIA AND BRONCHOGENIC CARCINOMA ASSOCIATED WITH RENAL EXCRETION OF LARGE AMOUNTS OF ANTIDIURETIC MATERIAL. Am J Med. 1963 Aug;35:257–268. doi: 10.1016/0002-9343(63)90217-1. [DOI] [PubMed] [Google Scholar]
  20. Taylor A. A., Davis J. O., Johnson J. A. Control of deoxycorticosterone secretion in the dog. Am J Physiol. 1972 Aug;223(2):466–472. doi: 10.1152/ajplegacy.1972.223.2.466. [DOI] [PubMed] [Google Scholar]
  21. WILLIAMS R. T. Carcinoma of bronchus with hyponatraemia and dermatomyositis. Br Med J. 1963 Jan 26;1(5325):233–236. doi: 10.1136/bmj.1.5325.233. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES