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Jensen JM, Mose FH, Kulik AE, et al. Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment. World J Nephrol. 2015;4(3):423-37doi: 10.5527/wjn.v4.i3.423.
Jensen, J. M., Mose, F. H., Kulik, A. E., Bech, J. N., Fenton, R. A., & Pedersen, E. B. (2015). Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment. World journal of nephrology, 4(3), 423-37. https://doi.org/10.5527/wjn.v4.i3.423
Jensen, Janni M, et al. "Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment." World journal of nephrology vol. 4,3 (2015): 423-37. doi: https://doi.org/10.5527/wjn.v4.i3.423
Jensen JM, Mose FH, Kulik AE, Bech JN, Fenton RA, Pedersen EB. Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment. World J Nephrol. 2015 Jul 06;4(3):423-37. doi: 10.5527/wjn.v4.i3.423. PMID: 26167467; PMCID: PMC4491934.
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World J Nephrol. 2015 Jul 06;4(3):423-37. doi: 10.5527/wjn.v4.i3.423.

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment.

World journal of nephrology

Janni M Jensen, Frank H Mose, Anna-Ewa O Kulik, Jesper N Bech, Robert A Fenton, Erling B Pedersen

Affiliations

  1. Janni M Jensen, Frank H Mose, Anna-Ewa O Kulik, Jesper N Bech, Erling B Pedersen, University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital, Regional Hospital Jutland West and Aarhus University, 7500 Holstebro, Denmark.

PMID: 26167467 PMCID: PMC4491934 DOI: 10.5527/wjn.v4.i3.423

Abstract

AIM: To quantify changes in urinary excretion of aquaporin2 water channels (u-AQP2), the sodium-potassium-chloride co-transporter (u-NKCC2) and the epithelial sodium channels (u-ENaC) during treatment with bendroflumethiazide (BFTZ), amiloride and placebo.

METHODS: In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fluid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with (51)Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC (u-ENaCγ), and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin II (p-ANG II) and aldosterone (p-Aldo) were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fluid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman's two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.

RESULTS: At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang II and p-Aldo were increased during active treatments (P < 0.001). After hypertonic saline, u-NKCC2 increased during amiloride (6% ± 34%; P = 0.081) and increased significantly during placebo (17% ± 24%; P = 0.010). U-AQP2 increased significantly during amiloride (31% ± 22%; P < 0.001) and placebo (34% ± 27%; P < 0.001), while u-NKCC2 and u-AQP2 did not change significantly during BFTZ (-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261). U- ENaCγ increased in all three groups (P < 0.050). PRC, AngII and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ (P = 0.048). cDBP decreased significantly during BFTZ (P < 0.001), but not during amiloride or placebo. There were no significant differences in body fluid volumes.

CONCLUSION: After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.

Keywords: Amiloride; Aquaporin2; Epithelial sodium channels; Hypertonic saline; Sodium; Sodium transporters; Sodium-potassium-chloride co-transporter; Thiazide; Urine; Water

References

  1. Kidney Int. 2011 Feb;79(4):423-31 - PubMed
  2. Pflugers Arch. 2009 May;458(1):111-35 - PubMed
  3. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8984-8 - PubMed
  4. J Biol Chem. 2003 Jul 18;278(29):26946-51 - PubMed
  5. Am J Physiol Renal Physiol. 2009 Nov;297(5):F1411-8 - PubMed
  6. Nephrol Dial Transplant. 2010 Aug;25(8):2502-10 - PubMed
  7. Am J Pathol. 2013 Jan;182(1):96-106 - PubMed
  8. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73 - PubMed
  9. Expert Rev Cardiovasc Ther. 2010 Jun;8(6):793-802 - PubMed
  10. N Engl J Med. 1995 Jun 8;332(23):1540-5 - PubMed
  11. Clin Sci (Lond). 1986 Apr;70(4):379-87 - PubMed
  12. Am J Physiol Renal Physiol. 2001 May;280(5):F860-7 - PubMed
  13. Am J Physiol Renal Physiol. 2014 Feb 15;306(4):F457-67 - PubMed
  14. BMC Nephrol. 2014 Jun 26;15:101 - PubMed
  15. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1013-7 - PubMed
  16. J Biol Chem. 2007 Mar 2;282(9):6455-62 - PubMed
  17. J Clin Invest. 1965 Jul;44:1160-70 - PubMed
  18. Exp Cell Res. 2012 May 15;318(9):1020-6 - PubMed
  19. Am J Physiol Renal Physiol. 2012 Jan 15;302(2):F264-75 - PubMed
  20. J Membr Biol. 1988 Oct;105(1):1-21 - PubMed
  21. J Clin Endocrinol Metab. 1997 Jun;82(6):1823-7 - PubMed
  22. PLoS One. 2012;7(9):e46593 - PubMed
  23. Physiology (Bethesda). 2011 Apr;26(2):115-23 - PubMed
  24. BMC Nephrol. 2013 Sep 26;14:202 - PubMed
  25. J Am Soc Nephrol. 2005 Jul;16(7):1920-8 - PubMed
  26. Circulation. 1968 Jan;37(1):45-53 - PubMed
  27. J Am Soc Nephrol. 2008 Sep;19(9):1721-31 - PubMed
  28. J Am Soc Nephrol. 1997 Sep;8(9):1357-62 - PubMed
  29. Physiol Rev. 1997 Apr;77(2):359-96 - PubMed
  30. Am J Physiol. 1993 Mar;264(3 Pt 2):F565-74 - PubMed
  31. Kidney Int. 2003 Apr;63(4):1417-25 - PubMed
  32. J Gen Physiol. 1993 Jul;102(1):25-42 - PubMed
  33. J Am Soc Hypertens. 2008 Mar-Apr;2(2):106-15 - PubMed
  34. PLoS One. 2013;8(3):e59371 - PubMed
  35. Acta Physiol Scand. 1999 May;166(1):23-30 - PubMed
  36. J Clin Invest. 1999 Oct;104(7):R19-23 - PubMed
  37. Am J Physiol. 1983 Apr;244(4):F355-66 - PubMed
  38. J Surg Res. 2003 Jul;113(1):6-12 - PubMed
  39. Physiol Meas. 2006 Sep;27(9):921-33 - PubMed
  40. J Am Soc Nephrol. 1999 Jul;10(7):1416-29 - PubMed
  41. Exp Neurol. 2001 Oct;171(2):227-34 - PubMed
  42. Am J Physiol Renal Physiol. 2013 Jan 15;304(2):F222-32 - PubMed
  43. Hypertension. 2009 Aug;54(2):196-202 - PubMed
  44. Clin Exp Hypertens. 2013;35(5):313-24 - PubMed
  45. Kidney Int. 2006 Jan;69(2):304-12 - PubMed
  46. Nephrol Dial Transplant. 1993;8(10):1064-70 - PubMed
  47. Scand J Clin Lab Invest. 2012 Feb;72(1):78-86 - PubMed
  48. Med Princ Pract. 2012;21(2):101-14 - PubMed
  49. Kidney Int. 2005 Mar;67(3):1010-8 - PubMed
  50. Kidney Int. 2010 Nov;78(9):849-56 - PubMed
  51. BMC Nephrol. 2010 Oct 28;11:28 - PubMed
  52. Am J Physiol Renal Physiol. 2000 Jul;279(1):F46-53 - PubMed
  53. Cell Mol Life Sci. 2012 Mar;69(5):683-95 - PubMed
  54. J Am Soc Nephrol. 1996 Mar;7(3):403-9 - PubMed
  55. Biochim Biophys Acta. 2010 Dec;1802(12):1166-77 - PubMed
  56. Am J Physiol Renal Physiol. 2001 Jun;280(6):F1093-106 - PubMed
  57. Kidney Int. 1995 Oct;48(4):1057-68 - PubMed

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