Transport proteins in the inner medullas of diabetic kidneys are further increased by candesartan.

Abstract

Dilute urine is a problem in uncontrolled diabetes mellitus (DM). Angiotensin II (AngII) receptor blockers ie. candesartan slow chronic kidney disease in DM patients. We investigated UT‐A1, UT‐A3, NKCC2, and AQP2 in control +/− candesartan rats and 3‐week DM +/− candesartan 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 blot analysis showed that in inner medullary (IM) tip and base, UT‐A1 expression was increased in DM rats compared to controls (Tip: 158±13%, Base: 120±25). UT‐A3 abundance was increased in both IM tip (123±11%) and base (146±17%) of DM rats vs controls (100%). UT‐A3 was unchanged in candesartan‐treated control rats. In candesartan treated DM rats UT‐A3 increased (IM tip: 160±14%; base 210±19%). Candesartan treated DM rats had slightly higher AQP2 in IM (46%, p<0.05) vs control rats. NKCC2 was increased 45±10% in OM of DM vs control rats. While candesartan did not alter NKCC2 in controls, NKCC2 was increased a further 41% by candesartan treatment in DM 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 AngII receptor blockers in diabetes.