Abstract
Diabetes is associated with increased activity of the renal renin angiotensin system (RAS). Previously, we demonstrated that streptozotocin (STZ)-induced diabetic rats have significantly increased abundances of renal distal sodium transporters and channels, e.g., the thiazide-sensitive Na-Cl cotransporter (NCC) and the epithelial sodium channel (ENaC). To determine the role of elevated RAS activity in these changes, male Sprague-Dawley rats (100–150 g) were made diabetic by intravenous injection of STZ (65 mg/kg·bw) or treated with vehicle (n = 12/group). Rats were fed standard 1% NaCl rodent chow and watered ad libitum. After 14 days, rats were further divided (n = 6/group) to receive candesartan in the drinking water (2 mg/kg/day) or plain water for 7 additional days. Immunoblotting revealed, in cortex, diabetes caused a modest increase in NCC, β- and γ-ENaC (85-kDa band) abundances (band density ~ 150% of non-diabetic controls). Candesartan not only reversed these increases, but significantly reduced abundance of NCC and ENaC subunits to ~50% of non-candesartan-treated rats in both diabetic and non-diabetic rats. In contrast, in the medulla, diabetes caused a much greater increase in ENaC subunits and α-1-Na-K-ATPase (band densities 200–600% of non-diabetic controls) and these increases were irreversible by candesartan. Moreover, candesartan increased β- and γ-ENaC in the non-diabetic rats, in the medulla tip. Thus the increased abundances of sodium transporters in the cortex, but not the medulla, with diabetes, are candesartan-sensitive, and therefore, likely due to enhanced AT1-mediated signaling.
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