{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:16:47Z","timestamp":1778275007293,"version":"3.51.4"},"reference-count":14,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p> 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 \u00b1 0.06 nM) and candesartan-treated rats (0.34 \u00b1 0.14 nM) were the same. DM rats had higher aldosterone levels (1.48 \u00b1 0.37 nM) that were decreased by candesartan (0.97 \u00b1 0.26 nM). Western analysis showed that UT-A1 expression was increased in DM rats compared with controls in inner medullary (IM) tip (158 \u00b1 13%) and base (120 \u00b1 25%). UT-A3 abundance was increased in IM tip (123 \u00b1 11%) and base (146 \u00b1 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 \u00b1 14%) and base (210 \u00b1 19%). Candesartan-treated DM rats had slightly higher AQP2 in IM (46%, P &lt; 0.05) vs. control rats. NKCC2\/BSC1 was increased 145 \u00b1 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. <\/jats:p>","DOI":"10.1152\/ajprenal.00600.2007","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T00:55:04Z","timestamp":1208393704000},"page":"F1448-F1452","source":"Crossref","is-referenced-by-count":16,"title":["Candesartan augments compensatory changes in medullary transport proteins in the diabetic rat kidney"],"prefix":"10.1152","volume":"294","author":[{"given":"Mitsi A.","family":"Blount","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff M.","family":"Sands","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimilia J.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tekla D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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