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. 1988 Nov;82(5):1624–1632. doi: 10.1172/JCI113774

Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.

T D DuBose Jr 1, C R Caflisch 1
PMCID: PMC442731  PMID: 3183058

Abstract

Mineralocorticoid plays a role in urinary acidification and acid-base balance, but the response of the inner medulla to aldosterone has not been elucidated. A model of selective aldosterone deficiency (SAD) with hyperkalemia and hyperchloremic metabolic acidosis was employed to assess segmental acidification by measuring in situ pH, titratable acidity (TA) and total ammonia (Am). Hydrogen ion secretion was also examined as a function of the increment in in situ PCO2 in the collecting duct during bicarbonate loading. SAD rats were compared to ADX controls that received adrenalectomy and chronic replacement of gluco- and mineralocorticoid and to rats with chronic metabolic acidosis induced by oral NH4Cl (CMA). Both fractional and absolute delivery of Am to the loop of Henle was lower in SAD vs. CMA rats (1.34 to 3.63 mM, P less than 0.01). Delivery of Am to the base and tip collecting duct (BCD and TCD) was also markedly lower in SAD (1.50 vs. 0.52 and 1.77 vs. 0.47 mM, respectively, P less than 0.01). Net addition of Am and net acid between BCD and TCD, observed in CMA rats, was not observed in SAD despite equivalent degrees of systemic metabolic acidosis. Similarly, the concentration gradient favoring transfer of NH3 between loop of Henle and CD was reduced in SAD. During bicarbonate loading the increment in PCO2 at BCD, TCD and in final urine was significantly lower in SAD rats than in adrenal intact bicarbonate-loaded rats. Therefore, the acidification defect in this model of SAD appears to be a result of a decrease in ammonia production and delivery to the loop of Henle, impaired transfer from loop to collecting duct and reduction in the rate of H+ secretion by the collecting duct.

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Selected References

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  1. Al-Awqati Q., Norby L. H., Mueller A., Steinmetz P. R. Characteristics of stimulation of H+ transport by aldosterone in turtle urinary bladder. J Clin Invest. 1976 Aug;58(2):351–358. doi: 10.1172/JCI108479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arruda J. A., Subbarayudu K., Dytko G., Mola R., Kurtzman N. A. Voltage-dependent distal acidification defect induced by amiloride. J Lab Clin Med. 1980 Mar;95(3):407–416. [PubMed] [Google Scholar]
  3. Buerkert J., Martin D., Trigg D. Ammonium handling by superficial and juxtamedullary nephrons in the rat. Evidence for an ammonia shunt between the loop of Henle and the collecting duct. J Clin Invest. 1982 Jul;70(1):1–12. doi: 10.1172/JCI110581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buerkert J., Martin D., Trigg D. Segmental analysis of the renal tubule in buffer production and net acid formation. Am J Physiol. 1983 Apr;244(4):F442–F454. doi: 10.1152/ajprenal.1983.244.4.F442. [DOI] [PubMed] [Google Scholar]
  5. Chan J. C. The rapid determination of urinary titratable acid and ammonium and evaluation of freezing as a method of preservation. Clin Biochem. 1972 Jun;5(2):94–98. doi: 10.1016/s0009-9120(72)80014-6. [DOI] [PubMed] [Google Scholar]
  6. DiTella P. J., Sodhi B., McCreary J., Arruda J. A., Kurtzman N. A. Mechanism of the metabolic acidosis of selective mineralocorticoid deficiency. Kidney Int. 1978 Nov;14(5):466–477. doi: 10.1038/ki.1978.151. [DOI] [PubMed] [Google Scholar]
  7. DuBose T. D., Jr, Caflisch C. R. Validation of the difference in urine and blood carbon dioxide tension during bicarbonate loading as an index of distal nephron acidification in experimental models of distal renal tubular acidosis. J Clin Invest. 1985 Apr;75(4):1116–1123. doi: 10.1172/JCI111805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DuBose T. D., Jr Hydrogen ion secretion by the collecting duct as a determinant of the urine to blood PCO2 gradient in alkaline urine. J Clin Invest. 1982 Jan;69(1):145–156. doi: 10.1172/JCI110425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DuBose T. D., Jr, Lucci M. S., Hogg R. J., Pucacco L. R., Kokko J. P., Carter N. W. Comparison of acidification parameters in superficial and deep nephrons of the rat. Am J Physiol. 1983 May;244(5):F497–F503. doi: 10.1152/ajprenal.1983.244.5.F497. [DOI] [PubMed] [Google Scholar]
  10. Good D. W., Burg M. B. Ammonia production by individual segments of the rat nephron. J Clin Invest. 1984 Mar;73(3):602–610. doi: 10.1172/JCI111250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Good D. W., Caflisch C. R., DuBose T. D., Jr Transepithelial ammonia concentration gradients in inner medulla of the rat. Am J Physiol. 1987 Mar;252(3 Pt 2):F491–F500. doi: 10.1152/ajprenal.1987.252.3.F491. [DOI] [PubMed] [Google Scholar]
  12. Good D. W., DuBose T. D., Jr Ammonia transport by early and late proximal convoluted tubule of the rat. J Clin Invest. 1987 Mar;79(3):684–691. doi: 10.1172/JCI112871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Good D. W. Effects of potassium on ammonia transport by medullary thick ascending limb of the rat. J Clin Invest. 1987 Nov;80(5):1358–1365. doi: 10.1172/JCI113213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Higashihara E., Carter N. W., Pucacco L., Kokko J. P. Aldosterone effects on papillary collecting duct pH profile of the rat. Am J Physiol. 1984 May;246(5 Pt 2):F725–F731. doi: 10.1152/ajprenal.1984.246.5.F725. [DOI] [PubMed] [Google Scholar]
  15. Hulter H. N., Ilnicki L. P., Harbottle J. A., Sebastian A. Impaired renal H+ secretion and NH3 production in mineralocorticoid-deficient glucocorticoid-replete dogs. Am J Physiol. 1977 Feb;232(2):F136–F146. doi: 10.1152/ajprenal.1977.232.2.F136. [DOI] [PubMed] [Google Scholar]
  16. Hulter H. N., Licht J. H., Glynn R. D., Sebastian A. Renal acidosis in mineralocorticoid deficiency is not dependent on NaCl depletion or hyperkalemia. Am J Physiol. 1979 Mar;236(3):F283–F294. doi: 10.1152/ajprenal.1979.236.3.F283. [DOI] [PubMed] [Google Scholar]
  17. JORGENSEN K. Titrimetric determination of the net excretion of acid/base in urine. Scand J Clin Lab Invest. 1957;9(3):287–291. doi: 10.3109/00365515709079972. [DOI] [PubMed] [Google Scholar]
  18. Karlmark B., Jaeger P., Fein H., Giebisch G. Coulometric acid-base titration in nanoliter samples with glass and antimony electrodes. Am J Physiol. 1982 Jan;242(1):F95–F99. doi: 10.1152/ajprenal.1982.242.1.F95. [DOI] [PubMed] [Google Scholar]
  19. Kleinman J. G., Blumenthal S. S., Wiessner J. H., Reetz K. L., Lewand D. L., Mandel N. S., Mandel G. S., Garancis J. C., Cragoe E. J., Jr Regulation of pH in rat papillary tubule cells in primary culture. J Clin Invest. 1987 Dec;80(6):1660–1669. doi: 10.1172/JCI113255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurtzman N. A. "Short-circuit" renal tubular acidosis. J Lab Clin Med. 1980 May;95(5):633–636. [PubMed] [Google Scholar]
  21. Laski M. E., Kurtzman N. A. Characterization of acidification in the cortical and medullary collecting tubule of the rabbit. J Clin Invest. 1983 Dec;72(6):2050–2059. doi: 10.1172/JCI111170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martin R. S., Jones W. J., Hayslett J. P. Animal model to study the effect of adrenal hormones on epithelial function. Kidney Int. 1983 Sep;24(3):386–391. doi: 10.1038/ki.1983.171. [DOI] [PubMed] [Google Scholar]
  23. Nagami G. T., Sonu C. M., Kurokawa K. Ammonia production by isolated mouse proximal tubules perfused in vitro. Effect of metabolic acidosis. J Clin Invest. 1986 Jul;78(1):124–129. doi: 10.1172/JCI112540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. O'Neil R. G., Helman S. I. Transport characteristics of renal collecting tubules: influences of DOCA and diet. Am J Physiol. 1977 Dec;233(6):F544–F558. doi: 10.1152/ajprenal.1977.233.6.F544. [DOI] [PubMed] [Google Scholar]
  25. Prigent A., Bichara M., Paillard M. Hydrogen transport in papillary collecting duct of rabbit kidney. Am J Physiol. 1985 Mar;248(3 Pt 1):C241–C246. doi: 10.1152/ajpcell.1985.248.3.C241. [DOI] [PubMed] [Google Scholar]
  26. Richardson R. M., Kunau R. T., Jr Bicarbonate reabsorption in the papillary collecting duct: effect of acetazolamide. Am J Physiol. 1982 Jul;243(1):F74–F80. doi: 10.1152/ajprenal.1982.243.1.F74. [DOI] [PubMed] [Google Scholar]
  27. Robson W. L., Halperin M. L., Stinebaugh B. J., Goldstein M. B. Effect of mineralocorticoids on collecting duct hydrogen ion secretion in the rabbit. Can J Physiol Pharmacol. 1981 Mar;59(3):235–238. doi: 10.1139/y81-037. [DOI] [PubMed] [Google Scholar]
  28. Sebastian A., Schambelan M., Lindenfeld S., Morris R. C., Jr Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism. N Engl J Med. 1977 Sep 15;297(11):576–583. doi: 10.1056/NEJM197709152971104. [DOI] [PubMed] [Google Scholar]
  29. Sebastian A., Sutton J. M., Hulter H. N., Schambelan M., Poler S. M. Effect of mineralocorticoid replacement therapy on renal acid-base homeostasis in adrenalectomized patients. Kidney Int. 1980 Dec;18(6):762–773. doi: 10.1038/ki.1980.195. [DOI] [PubMed] [Google Scholar]
  30. Stokes J. B., Ingram M. J., Williams A. D., Ingram D. Heterogeneity of the rabbit collecting tubule: localization of mineralocorticoid hormone action to the cortical portion. Kidney Int. 1981 Sep;20(3):340–347. doi: 10.1038/ki.1981.144. [DOI] [PubMed] [Google Scholar]
  31. Stone D. K., Seldin D. W., Kokko J. P., Jacobson H. R. Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect. J Clin Invest. 1983 Jul;72(1):77–83. doi: 10.1172/JCI110986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Szylman P., Better O. S., Chaimowitz C., Rosler A. Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. N Engl J Med. 1976 Feb 12;294(7):361–365. doi: 10.1056/NEJM197602122940703. [DOI] [PubMed] [Google Scholar]
  33. Tannen R. L., McGill J. Influence of potassium on renal ammonia production. Am J Physiol. 1976 Oct;231(4):1178–1184. doi: 10.1152/ajplegacy.1976.231.4.1178. [DOI] [PubMed] [Google Scholar]
  34. Welbourne T. C., Francoeur D. Influence of aldosterone on renal ammonia production. Am J Physiol. 1977 Jul;233(1):E56–E60. doi: 10.1152/ajpendo.1977.233.1.E56. [DOI] [PubMed] [Google Scholar]
  35. Wilcox C. S., Cemerikic D. A., Giebisch G. Differential effects of acute mineralo- and glucocorticosteroid administration on renal acid elimination. Kidney Int. 1982 Apr;21(4):546–556. doi: 10.1038/ki.1982.61. [DOI] [PubMed] [Google Scholar]

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