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Author Notes:

Address for reprint requests and other correspondence: J. Klein, Emory Univ. School of Medicine, Renal Division, 1639 Pierce Drive, NE, WMB Rm. 3319B, Atlanta, GA 30322 (e-mail: janet.klein@emory.edu)

Subject:

Research Funding:

This work was supported by National Institutes of Health Grants R01-DK-62081 and R01-DK-412707, an American Heart Association Grant-in-Aid 0655280B and Postdoctoral Fellowship Grant, and the Cottrell Fellowship of Emory University.

Keywords:

  • angiotensin II
  • UT-A urea transporter
  • aquaporin
  • AQP2
  • NKCC2

Candesartan augments compensatory changes in medullary transport proteins in the diabetic rat kidney

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Journal Title:

American Journal of Physiology - Renal Physiology

Volume:

Volume 294, Number 6

Publisher:

, Pages F1448-F1452

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Volume depletion due to persistent glucosuria-induced osmotic diuresis is a significant problem in uncontrolled diabetes mellitus (DM). Angiotensin II receptor blockers (ARBs), such as candesartan, slow the progression of chronic kidney disease in patients with DM. However, mice with genetic knockout of components of the renin-angiotensin system have urine concentrating defects, suggesting that ARBs may exacerbate the volume depletion. Therefore, the effect of candesartan on UT-A1, UT-A3, NKCC2, and aquaporin-2 (AQP2) protein abundances was determined in control and 3-wk DM rats. Aldosterone levels in control rats (0.36 ± 0.06 nM) and candesartan-treated rats (0.34 ± 0.14 nM) were the same. DM rats had higher aldosterone levels (1.48 ± 0.37 nM) that were decreased by candesartan (0.97 ± 0.26 nM). Western analysis showed that UT-A1 expression was increased in DM rats compared with controls in inner medullary (IM) tip (158 ± 13%) and base (120 ± 25%). UT-A3 abundance was increased in IM tip (123 ± 11%) and base (146 ± 17%) of DM rats vs. controls. UT-A3 was unchanged in candesartan-treated control rats. In candesartan-treated DM rats, UT-A3 increased in IM tip (160 ± 14%) and base (210 ± 19%). Candesartan-treated DM rats had slightly higher AQP2 in IM (46%, P < 0.05) vs. control rats. NKCC2/BSC1 was increased 145 ± 10% in outer medulla of DM vs. control rats. We conclude that candesartan augments compensatory changes in medullary transport proteins, reducing the losses of solute and water during uncontrolled DM. These changes may represent a previously unrecognized beneficial effect of type 1 ARBs in DM.

Copyright information:

© 2008, American Physiological Society

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