Angiotensin-(1-7) is a ligand for the Mas receptor and may protect against tissue injury associated with renin-angiotensin system activation. We determined the effects of endogenous or exogenous angiotensin-(1-7) in mice with unilateral ureteral obstruction (UUO). Mice with UUO were treated with or without the angiotensin-(1-7) antagonist A779 or with 6， 24， or 62 μg/kg per hour exogenous angiotensin-(1-7). After 10 days， kidneys were harvested for histology， immunoblots， and measurement of NADPH oxidase. Compared with controls， A779 treatment significantly increased fibronectin， transforming growth factor-β， and α-smooth muscle actin expression in obstructed kidneys and enhanced tubulointers... More
Angiotensin-(1-7) is a ligand for the Mas receptor and may protect against tissue injury associated with renin-angiotensin system activation. We determined the effects of endogenous or exogenous angiotensin-(1-7) in mice with unilateral ureteral obstruction (UUO). Mice with UUO were treated with or without the angiotensin-(1-7) antagonist A779 or with 6， 24， or 62 μg/kg per hour exogenous angiotensin-(1-7). After 10 days， kidneys were harvested for histology， immunoblots， and measurement of NADPH oxidase. Compared with controls， A779 treatment significantly increased fibronectin， transforming growth factor-β， and α-smooth muscle actin expression in obstructed kidneys and enhanced tubulointerstitial injury， apoptosis， and NADPH oxidase. Unexpectedly， administration of angiotensin-(1-7) to mice with UUO caused injury in obstructed kidneys compared with controls and increased macrophage infiltration. In obstructed kidneys from mice with gene deletion of Mas (Mas(-/-))， apoptosis and macrophage infiltration were increased compared with wild-type mice. Angiotensin-(1-7) (but not A779) further increased apoptosis and macrophage influx in obstructed kidneys from Mas(-/-) mice， compared with untreated Mas(-/-) mice. These data indicate that endogenous angiotensin-(1-7) protects against kidney injury in UUO. In mice with or without the Mas receptor， however， delivery of exogenous angiotensin-(1-7) worsens kidney damage. The results suggest dose-dependent effects of angiotensin-(1-7) in the kidney in UUO， with endogenous angiotensin-(1-7) promoting repair pathways via interaction with Mas and higher amounts exacerbating injury.
