title: The effect of angiotensin-(1-7) in mouse unilateral ureteral obstruction.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Zimmerman
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zimpelmann
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Gutsol
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Rhian
authors.initials: R
authors.lastname: Touyz
authors.affiliation: Division of Nephrology, Department of Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: kburns@ottawahospital.on.ca.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Burns
mesh_terms: D000199:Actins / Q000378:metabolism; D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D005353:Fibronectins / Q000378:metabolism; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); D000199:Actins; D005353:Fibronectins; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)