Inhibition of NADPH oxidase improves renal autoregulation in rats fed a high salt diet

Previous work shows that a high salt diet (HS) blunts afferent arteriolar (AA) autoregulatory behavior by 83% partly through reactive oxygen species (ROS). Thus, we tested the hypothesis that HS blunts autoregulation by enhancing NADPH‐dependent ROS production. Rats were fed a normal (NS 0.8% NaCl) or HS (8% NaCl) diet for 14 days. A subset of rats, received the NADPH oxidase inhibitor, apocynin (~25mg/kg/day) in the drinking water. Studies were performed in vivo to assess whole kidney autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) when left kidney perfusion pressure (PP) was reduced to ~95mmHg using an adjustable aortic clamp. Decreasing PP significantly reduced RBF in HS rats by 18%, from a baseline of 12.6 ±0.6 to 10.4±0.6 ml/min (n=8) compared to 2% in NS rats (8.3±0.8 to 8.1±0.9 ml/min; n=10; P<.05 vs. HS). Apocynin treatment improved autoregulatory behavior in HS rats with RBF declining by just 8%, from a baseline of 12.5 ±0.5 to 11.6 ±0.5 ml/min (n=11). Similarly, left kidney GFR declined by 27% (457 ± 24 vs. 335 ± 31 μl/min/100gbw; n=8) in HS rats compared to just 5% (496 ±46 vs. 470± 39 μl/min/100gbw; n=10) in NS rats. Apocynin improved GFR autoregulation in HS rats with only a 12% reduction at 95 mmHg (472±39 vs. 417±21 μl/min/100gbw; n=11). These data suggest that NADPH oxidase‐derived ROS impair renal autoregulatory behavior in rats fed a HS diet. Funding: NIH‐ HL098135 , NIH‐1PO1HL095499