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

American Journal of Physiology. Renal Physiology
Mitsi A BlountJanet D Klein

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-trea...Continue Reading

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Aug 10, 2007·American Journal of Physiology. Renal Physiology·Mitsi A BlountJeff M Sands

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Citations

Sep 26, 2012·Pflügers Archiv : European journal of physiology·Janet D KleinJeff M Sands
Sep 23, 2011·American Journal of Physiology. Renal Physiology·Karl P RoosDonald E Kohan
Jul 14, 2012·American Journal of Physiology. Renal Physiology·Tobias N von Bergen, Mitsi A Blount
Mar 17, 2020·American Journal of Physiology. Renal Physiology·Fitra RiantoJanet D Klein
Jan 15, 2016·American Journal of Physiology. Renal Physiology·Anita T LaytonAurélie Edwards
Sep 12, 2019·American Journal of Physiology. Renal Physiology·Hua SuChun Zhang

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