Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1983 Jan;71(1):55–65. doi: 10.1172/JCI110751

Effect of carbonic anhydrase inhibition on superficial and deep nephron bicarbonate reabsorption in the rat.

T D DuBose Jr, M S Lucci
PMCID: PMC436837  PMID: 6848559

Abstract

The nephron segment responsible for the acetazolamide-insensitive fraction of renal bicarbonate reabsorption has not been clearly delineated. This study compares superficial and deep nephron bicarbonate reabsorption before and after acetazolamide at two dose levels (20 and 50 mg/kg per h) in mutant Munich-Wistar rats employing both cortical and papillary micropuncture and microcalorimetry. Systemic acid-base balance and right whole kidney glomerular filtration rate were similar in all groups examined. The effects of the two doses of acetazolamide were indistinguishable and resulted in a significant increase in whole kidney bicarbonate excretion that compared favorably with the fraction delivered out of the left papillary tip. Acetazolamide inhibited superficial proximal bicarbonate reabsorption by 80.0%, whereas reabsorption up to the deep loop of Henle was decreased by only 52% (P less than 0.001). Bicarbonate reabsorption that was insensitive to acetazolamide occurred in the superficial and deep loop of Henle and between the distal tubule and base collecting duct. Because water reabsorption in these segments could serve to generate transepithelial bicarbonate concentration gradients favorable for reabsorption, we attempted to minimize water abstraction by combined administration of mannitol and acetazolamide. During this condition a significant increase in bicarbonate delivery up to the deep loop of Henle was noted (52 vs. 65%), whereas superficial nephron reabsorption was not altered. Furthermore, an outwardly directed bicarbonate concentration gradient from the deep loop of Henle to vasa recta was demonstrated during acetazolamide (delta tCO2 = 20.9 +/- 3.3 mM), but was abolished during combined mannitol and acetazolamide administration (delta tCO2 = 3.5 +/- 0.9 mM). It is concluded that carbonic anhydrase inhibition results in a disparate effect on nephron bicarbonate reabsorption when juxtamedullary and superficial nephron segments are compared. Our findings suggest that a mechanism for residual bicarbonate reabsorption during acetazolamide administration may be passive reabsorption driven by favorable transepithelial concentration gradients.

Full text

PDF
55

Images in this article

60Image
on p.60

Selected References

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

  1. 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]
  2. Burg M., Green N. Bicarbonate transport by isolated perfused rabbit proximal convoluted tubules. Am J Physiol. 1977 Oct;233(4):F307–F314. doi: 10.1152/ajprenal.1977.233.4.F307. [DOI] [PubMed] [Google Scholar]
  3. Cogan M. G., Maddox D. A., Lucci M. S., Rector F. C., Jr Control of proximal bicarbonate reabsorption in normal and acidotic rats. J Clin Invest. 1979 Nov;64(5):1168–1180. doi: 10.1172/JCI109570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cogan M. G., Maddox D. A., Warnock D. G., Lin E. T., Rector F. C., Jr Effect of acetazolamide on bicarbonate reabsorption in the proximal tubule of the rat. Am J Physiol. 1979 Dec;237(6):F447–F454. doi: 10.1152/ajprenal.1979.237.6.F447. [DOI] [PubMed] [Google Scholar]
  5. Cogan M. G., Rector F. C., Jr Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition. Am J Physiol. 1982 Mar;242(3):F274–F284. doi: 10.1152/ajprenal.1982.242.3.F274. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. DuBose T. D., Jr, Pucacco L. R., Carter N. W. Determination of disequilibrium pH in the rat kidney in vivo: evidence of hydrogen secretion. Am J Physiol. 1981 Feb;240(2):F138–F146. doi: 10.1152/ajprenal.1981.240.2.F138. [DOI] [PubMed] [Google Scholar]
  8. DuBose T. D., Jr, Pucacco L. R., Lucci M. S., Carter N. W. Micropuncture determination of pH, PCO2, and total CO2 concentration in accessible structures of the rat renal cortex. J Clin Invest. 1979 Aug;64(2):476–482. doi: 10.1172/JCI109485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DuBose T. D., Jr, Seldin D. W., Kokko J. P. Segmental chloride reabsorption in the rat nephron as a function of load. Am J Physiol. 1978 Feb;234(2):F97–105. doi: 10.1152/ajprenal.1978.234.2.F97. [DOI] [PubMed] [Google Scholar]
  10. Gelbart D. R., Battilana C. A., Bhattacharya J., Lacy F. B., Jamison R. L. Transepithelial gradient and fractional delivery of chloride in thin loop of Henle. Am J Physiol. 1978 Sep;235(3):F192–F198. doi: 10.1152/ajprenal.1978.235.3.F192. [DOI] [PubMed] [Google Scholar]
  11. Higashihara E., Stokes J. B., Kokko J. P., Campbell W. B., DuBose T. D., Jr Cortical and papillary micropuncture examination of chloride transport in segments of the rat kidney during inhibition of prostaglandin production. Possible role for prostaglandins in the chloruresis of acute volume expansion. J Clin Invest. 1979 Nov;64(5):1277–1287. doi: 10.1172/JCI109583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holmberg C., Kokko J. P., Jacobson H. R. Determination of chloride and bicarbonate permeabilities in proximal convoluted tubules. Am J Physiol. 1981 Oct;241(4):F386–F394. doi: 10.1152/ajprenal.1981.241.4.F386. [DOI] [PubMed] [Google Scholar]
  13. Imai M. Function of the thin ascending limb of Henle of rats and hamsters perfused in vitro. Am J Physiol. 1977 Mar;232(3):F201–F209. doi: 10.1152/ajprenal.1977.232.3.F201. [DOI] [PubMed] [Google Scholar]
  14. Jacobson H. R. Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules. Am J Physiol. 1981 Jan;240(1):F54–F62. doi: 10.1152/ajprenal.1981.240.1.F54. [DOI] [PubMed] [Google Scholar]
  15. Lucci M. S., Pucacco L. R., Carter N. W., DuBose T. D., Jr Evaluation of bicarbonate transport in rat distal tubule: effects of acid-base status. Am J Physiol. 1982 Oct;243(4):F335–F341. doi: 10.1152/ajprenal.1982.243.4.F335. [DOI] [PubMed] [Google Scholar]
  16. Lucci M. S., Pucacco L. R., DuBose T. D., Jr, Kokko J. P., Carter N. W. Direct evaluation of acidification by rat proximal tubule: role of carbonic anhydrase. Am J Physiol. 1980 May;238(5):F372–F379. doi: 10.1152/ajprenal.1980.238.5.F372. [DOI] [PubMed] [Google Scholar]
  17. Lucci M. S., Warnock D. G., Rector F. C., Jr Carbonic anhydrase-dependent bicarbonate reabsorption in the rat proximal tubule. Am J Physiol. 1979 Jan;236(1):F58–F65. doi: 10.1152/ajprenal.1979.236.1.F58. [DOI] [PubMed] [Google Scholar]
  18. Lönnerholm G., Ridderstråle Y. Intracellular distribution of carbonic anhydrase in the rat kidney. Kidney Int. 1980 Feb;17(2):162–174. doi: 10.1038/ki.1980.20. [DOI] [PubMed] [Google Scholar]
  19. Maren T. H. Carbon dioxide equilibria in the kidney: the problems of elevated carbon dioxide tension, delayed dehydration, and disequilibrium pH. Kidney Int. 1978 Nov;14(5):395–405. doi: 10.1038/ki.1978.144. [DOI] [PubMed] [Google Scholar]
  20. Maren T. H. Chemistry of the renal reabsorption of bicarbonate. Can J Physiol Pharmacol. 1974 Dec;52(6):1041–1050. doi: 10.1139/y74-138. [DOI] [PubMed] [Google Scholar]
  21. Mathisen O., Raeder M., Sejersted O. M., Kiil F. Effect of acetazolamide on glomerular balance and renal metabolic rate. Scand J Clin Lab Invest. 1976 Nov;36(7):617–625. doi: 10.3109/00365517609054486. [DOI] [PubMed] [Google Scholar]
  22. McKinney T. D., Burg M. B. Biocarbonate and fluid absorption by renal proximal straight tubules. Kidney Int. 1977 Jul;12(1):1–8. doi: 10.1038/ki.1977.72. [DOI] [PubMed] [Google Scholar]
  23. RECTOR F. C., Jr, CARTER N. W., SELDIN D. W. THE MECHANISM OF BICARBONATE REABSORPTION IN THE PROXIMAL AND DISTAL TUBULES OF THE KIDNEY. J Clin Invest. 1965 Feb;44:278–290. doi: 10.1172/JCI105142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Vieira F. L., Malnic G. Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode. Am J Physiol. 1968 Apr;214(4):710–718. doi: 10.1152/ajplegacy.1968.214.4.710. [DOI] [PubMed] [Google Scholar]
  26. Vurek G. G., Warnock D. G., Corsey R. Measurement of picomole amounts of carbon dioxide by calorimetry. Anal Chem. 1975 Apr;47(4):765–767. doi: 10.1021/ac60354a024. [DOI] [PubMed] [Google Scholar]
  27. Warnock D. G., Burg M. B. Urinary acidification: CO2 transport by the rabbit proximal straight tubule. Am J Physiol. 1977 Jan;232(1):F20–F25. doi: 10.1152/ajprenal.1977.232.1.F20. [DOI] [PubMed] [Google Scholar]

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

RESOURCES