Physiological activation of Renal‐Angiotensin System (RAS) by low salt diet does not cause kidney injury

Abstract

While increased intrarenal angiotensin (Ang) II is implicated in the development of renal injury in AngII‐dependent hypertension, the changes that occur when Ang II is increased physiologically by low salt (LS) diet have not been delineated. To evaluate the effects of high intrarenal AngII on renal injury elicited by a physiological stimulus, a LS diet (0.03% NaCl, N=6) was given to SD rats for 13d and tissues were compared with rats fed a normal salt (NS) diet (0.3% NaCl, N=6) and rats chronically AngII infused (80ng/min x 13d; N=5). By day 12, SBP was not different from NS rats (118±4 vs. 113±2 mmHg) but was lower than AngII rats (175±10 mmHg). Plasma and kidney AngII levels were greater in rats fed a LS diet than rats with NS (Plasma:154±49 vs. 33±10 fmol/ml; Kidney: 435±57 vs. 265±12 fmol/g) and similar to those in AngII rats (179±56 fmol/ml; 408±196 fmol/g). Glomerular expansion, glomerular and tubular cell proliferation, and macrophage infiltration were not different or slightly less intense in kidneys from LS rats compared to NS rats. However, glomerular and tubulointerstitial fibrosis were greater in LS rats (p<0.05). In contrast, all these markers were markedly augmented in AngII‐infused rats (p<0.001). In conclusion, high intrarenal AngII due to LS diet causes only modest kidney injury changes suggesting that intrarenal AngII must synergize with other factors in AngII‐dependent hypertension to cause kidney injury.