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. 1973 Oct;52(10):2418–2427. doi: 10.1172/JCI107432

Micropuncture Study of Diuretic Effects on Sodium and Calcium Reabsorption in the Dog Nephron

B R Edwards 1, P G Baer 1, R A L Sutton 1, J H Dirks 1
PMCID: PMC302500  PMID: 4729040

Abstract

A close relationship has been observed between the clearance rates of sodium and calcium under a variety of diuretic conditions. The thiazide diuretics act differently in dissociating the renal tubular reabsorption of sodium and calcium. This phenomenon has been further investigated using recollection micropuncture and clearance techniques in a group of 14 dogs subjected to three consecutive experimental phases: expansion to 3% of body weight (BWt) with Ringer's solution, chlorothiazide infusion at 20 mg/kg/h, and furosemide in a prime of 10 mg/kg/ and a 10 mg/kg/h infusion. Diuretic losses were balanced with infusion of equal volumes of Ringer's solution throughout the experiment. Chlorothiazide increased the fractional excretion (FE) of sodium almost threefold while FECa was not significantly altered. Furosemide increased FENa and FECa to an approximately equal, and more marked, degree. This dissociation of sodium and calcium reabsorption after chlorothiazide was also evident in the superficial distal tubule, where (tubule fluid/plasma sodium) (TF/PNa) increased from 0.32 to 0.49 (P < 0.01) and TF/(ultrafiltrate)UFCa was unchanged (0.35-0.31). Furosemide markedly reduced the transtubular concentration gradient for both sodium (0.86) and calcium (0.94). TF/PInul in decreased progressively from 3.79 to 2.78 to 2.33 in three phases. In the late proximal tubule, chlorothiazide induced a fall of TF/PInul in from 1.57 to 1.44 (P < 0.01), but the ratio TF/UFCa: TF/PNa was unchanged. Furosemide had no significant proximal effect. It is concluded that acute administration of chlorothiazide reduces sodium reabsorption in the distal hephron, presumably the cortical diluting segment, without affecting calcium reabsorption.

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Selected References

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  1. Antoniou L. D., Eisner G. M., Slotkoff L. M., Lilienfield L. S. Relationship between sodium and calcium transport in the kidney. J Lab Clin Med. 1969 Sep;74(3):410–420. [PubMed] [Google Scholar]
  2. Bennett C. M., Brenner B. M., Berliner R. W. Micropuncture study of nephron function in the rhesus monkey. J Clin Invest. 1968 Jan;47(1):203–216. doi: 10.1172/JCI105710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner B. M., Keimowitz R. I., Wright F. S., Berliner R. W. An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron. J Clin Invest. 1969 Feb;48(2):290–300. doi: 10.1172/JCI105985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brickman A. S., Massry S. G., Coburn J. W. changes in serum and urinary calcium during treatment with hydrochlorothiazide: studies on mechanisms. J Clin Invest. 1972 Apr;51(4):945–954. doi: 10.1172/JCI106889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brunette M., Wen S. F., Evanson R. L., Dirks J. H. Micropuncture study of magnesium reabsorption in the proximal tubule of the dog. Am J Physiol. 1969 Jun;216(6):1510–1516. doi: 10.1152/ajplegacy.1969.216.6.1510. [DOI] [PubMed] [Google Scholar]
  6. DICKER S. E., EGGLETON M. G. THE ANTIDIURETIC ACTION OF HYDROCHLOROTHIAZIDE IN THE HYDRATED RAT. J Physiol. 1964 Jun;171:377–383. doi: 10.1113/jphysiol.1964.sp007383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DUARTE C. G., BLAND J. H. CALCIUM, PHOSPHORUS AND URIC ACID CLEARANCES AFTER INTRAVENOUS ADMINISTRATION OF CHLOROTHIAZIDE. Metabolism. 1965 Mar;14:211–219. doi: 10.1016/0026-0495(65)90061-2. [DOI] [PubMed] [Google Scholar]
  8. DUARTE C. G., BLAND J. H. CHANGES IN METABOLISM OF CALCIUM, PHOSPHORUS AND URIC ACID AFTER ORAL ADMINISTRATION OF CHLOROTHIAZIDE. Metabolism. 1965 Aug;14:899–903. doi: 10.1016/0026-0495(65)90128-9. [DOI] [PubMed] [Google Scholar]
  9. Dirks J. H., Cirksena W. J., Berliner R. W. Micropuncture study of the effect of various diuretics on sodium reabsorption by the proximal tubules of the dog. J Clin Invest. 1966 Dec;45(12):1875–1885. doi: 10.1172/JCI105492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duarte C. G. Effects of chlorothiazide and amipramizide (MK 870) on the renal excretion of calcium, phosphate and magnesium. Metabolism. 1968 May;17(5):420–429. doi: 10.1016/0026-0495(68)90064-4. [DOI] [PubMed] [Google Scholar]
  11. Duarte C. G. Effects of ethacrynic acid and furosemide on urinary calcium, phosphate and magnesium. Metabolism. 1968 Oct;17(10):867–876. doi: 10.1016/0026-0495(68)90151-0. [DOI] [PubMed] [Google Scholar]
  12. Duarte C. G., Watson J. F. Calcium reabsorption in proximal tubule of the dog nephron. Am J Physiol. 1967 Jun;212(6):1355–1360. doi: 10.1152/ajplegacy.1967.212.6.1355. [DOI] [PubMed] [Google Scholar]
  13. EARLEY L. E., KAHN M., ORLOFF J. The effects of infusions of chlorothiazide on urinary dilution and concentration in the dog. J Clin Invest. 1961 May;40:857–866. doi: 10.1172/JCI104320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Edwards B. R., Novakova A., Sutton R. A., Dirks J. H. Effects of acute urea infusion on proximal tubular reabsorption in the dog kidney. Am J Physiol. 1973 Jan;224(1):73–79. doi: 10.1152/ajplegacy.1973.224.1.73. [DOI] [PubMed] [Google Scholar]
  15. Eknoyan G., Suki W. N., Martinez-Maldonado M. Effect of diuretics on urinary excretion of phosphate, calcium, and magnesium in thyroparathyroidectomized dogs. J Lab Clin Med. 1970 Aug;76(2):257–266. [PubMed] [Google Scholar]
  16. FUHR J., KACZMARCZYK J., KRUTTGEN C. D. Eine einfache colorimetrische Methode zur Inulinbestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin Wochenschr. 1955 Aug 1;33(29-30):729–730. doi: 10.1007/BF01473295. [DOI] [PubMed] [Google Scholar]
  17. Frederich A., Berger C., Gharib C. Influence d'un sulfamide diurétique, l'hydrochlorothiazide sur l'élimination urinaire du calcium. Therapie. 1965 May-Jun;20(3):695–707. [PubMed] [Google Scholar]
  18. HEINEMANN H. O., DEMARTINI F. E., LARAGH J. H. The effect of chlorothiazide on renal excretion of electrolytes and free water. Am J Med. 1959 Jun;26(6):853–861. doi: 10.1016/0002-9343(59)90207-4. [DOI] [PubMed] [Google Scholar]
  19. KESSLER R. H., HIERHOLZER K., GURD R. S., PITTS R. F. Localization of action of chlorothiazide in the nephron of the dog. Am J Physiol. 1959 Jun;196(6):1346–1351. doi: 10.1152/ajplegacy.1959.196.6.1346. [DOI] [PubMed] [Google Scholar]
  20. KIIL F. Permutation trial of diuretics. Chlorothiazide and hydroflumethiazide. Circulation. 1960 May;21:717–723. doi: 10.1161/01.cir.21.5.717. [DOI] [PubMed] [Google Scholar]
  21. LAMBERG B. A., KUHLBACK B. Effect of chlorothiazide and hydrochlorothiazide on the excretion of calcium in urine. Scand J Clin Lab Invest. 1959;11:351–357. doi: 10.3109/00365515909060464. [DOI] [PubMed] [Google Scholar]
  22. LICHTWITZ A., PARLIER R., de SEZE, HIOCO D., MIRAVET L. [The hypocalciuric effect of diuretic sulfonamides]. Sem Med Prof Med Soc. 1961 Aug 14;37:2350–2362. [PubMed] [Google Scholar]
  23. Marcus D. C., Jamison R. L. Photometric determination of picomole quantities of calcium. Anal Chem. 1972 Jul;44(8):1523–1525. doi: 10.1021/ac60316a020. [DOI] [PubMed] [Google Scholar]
  24. Meng K. Mikropunktionsuntersuchungen über die saluretische Wirkung von Hydrochlorothiazid, Acetazolamid und Furosemid. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1967;257(3):355–371. [PubMed] [Google Scholar]
  25. Morel F., Roinel N., Le Grimellec C. Electron probe analysis of tubular fluid composition. Nephron. 1969;6(3):350–364. doi: 10.1159/000179738. [DOI] [PubMed] [Google Scholar]
  26. Parfitt A. M. The acute effects of mersalyl, chlorothiazide and mannitol on the renal excretion of calcium and other ions in man. Clin Sci. 1969 Apr;36(2):267–282. [PubMed] [Google Scholar]
  27. Parfitt A. M. The interactions of thiazide diuretics with parathyroid hormone and vitamin D. Studies in patients with hypoparathyroidism. J Clin Invest. 1972 Jul;51(7):1879–1888. doi: 10.1172/JCI106990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Raman A. The calcium fractions of normal serum. Clin Biochem. 1971 Oct;4(3):141–146. doi: 10.1016/s0009-9120(71)91175-1. [DOI] [PubMed] [Google Scholar]
  29. SCHIRMEISTER J., WILLMANN H. UBER DIE HARNSAEURE- UND ANDERE CLEARANCES NACH INTRAVENOESER GABE VON FURSEMID BEIM MENSCHEN. Klin Wochenschr. 1964 Jul 1;42:623–628. doi: 10.1007/BF01480095. [DOI] [PubMed] [Google Scholar]
  30. SEITZ H., JAWORSKI Z. F. EFFECT OF HYDROCHLOROTHIAZIDE ON SERUM AND URINARY CALCIUM AND URINARY CITRATE. Can Med Assoc J. 1964 Feb 8;90:414–420. [PMC free article] [PubMed] [Google Scholar]
  31. SUKI W., RECTOR F. C., Jr, SELDIN D. W. THE SITE OF ACTION OF FUROSEMIDE AND OTHER SULFONAMIDE DIURETICS IN THE DOG. J Clin Invest. 1965 Sep;44:1458–1469. doi: 10.1172/JCI105252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Seely J. F., Dirks J. H. Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney. J Clin Invest. 1969 Dec;48(12):2330–2340. doi: 10.1172/JCI106199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seldin D. W., Eknoyan G., Suki W. N., Rector F. C., Jr Localization of diuretic action from the pattern of water and electrolyte excretion. Ann N Y Acad Sci. 1966 Nov 22;139(2):328–343. doi: 10.1111/j.1749-6632.1966.tb41207.x. [DOI] [PubMed] [Google Scholar]
  34. Sotorník I., Schück O., Stríbrná J. Influence of diuretics on renal calcium excretion. Experientia. 1969 Jun 15;25(6):591–592. doi: 10.1007/BF01896529. [DOI] [PubMed] [Google Scholar]
  35. Thurau K. Influence of sodium concentration at macula densa cells on tubular sodium load. Ann N Y Acad Sci. 1966 Nov 22;139(2):388–399. doi: 10.1111/j.1749-6632.1966.tb41212.x. [DOI] [PubMed] [Google Scholar]
  36. VANDER A. J., MALVIN R. L., WILDE W. S., SULLIVAN L. P. Localization of the site of action of chlorothiazide by stop-flow analysis. J Pharmacol Exp Ther. 1959 Jan;125(1):19–22. [PubMed] [Google Scholar]
  37. WALSER M. Calcium clearance as a function of sodium clearance in the dog. Am J Physiol. 1961 May;200:1099–1104. doi: 10.1152/ajplegacy.1961.200.5.1099. [DOI] [PubMed] [Google Scholar]
  38. WALSER M. Ion association. VII. Dependence of calciuresis on natriuresis during sulfate infusion. Am J Physiol. 1961 Nov;201:769–773. doi: 10.1152/ajplegacy.1961.201.5.769. [DOI] [PubMed] [Google Scholar]
  39. WESSON L. G., Jr Organic mercurial effects on renal tubular reabsorption of calcium and magnesium and on phosphate excretion in the dog. J Lab Clin Med. 1962 Apr;59:630–637. [PubMed] [Google Scholar]

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