The effect of angiotensin-(1-7) in mouse unilateral ureteral obstruction

Zimmerman, D. L., Zimpelmann, J., Xiao, F., Gutsol, A., Touyz, R. and Burns, K. D. (2015) The effect of angiotensin-(1-7) in mouse unilateral ureteral obstruction. American Journal of Pathology, 185(3), pp. 729-740. (doi: 10.1016/j.ajpath.2014.11.013) (PMID:25625676)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Zimmerman, D. L., Zimpelmann, J., Xiao, F., Gutsol, A., Touyz, R., and Burns, K. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:American Journal of Pathology
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
ISSN (Online):1525-2191

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