title: Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice.
abstract: Angiotensin II (Ang II) activates at least two receptors, AT1 and AT2, with the majority of its effects-such as vasoconstriction, inflammation, and matrix deposition-mediated by the AT1 receptor. It is thought that the AT2 receptor counteracts these processes; however, recent studies have found proinflammatory and hypertrophic effects of this receptor subtype. To identify the physiological roles of the AT2 receptor in chronic kidney disease, we performed renal ablation in AT2 receptor knockout and wild-type mice. Renal injury caused a greater impairment of renal function, glomerular injury, albuminuria, and mortality in the knockout mice than in the wild-type mice. There was increased fibronectin expression and inflammation in the knockout mice, as shown by augmented monocyte/macrophage infiltration and higher chemokine monocyte chemotactic protein-1 (MCP-1) and RANTES expression in the remnant kidney. The higher mortality and renal morbidity of the knockout mice was not due to differences in systemic blood pressure, glomerular volume, AT1 receptor, renin, or endothelial nitric oxide synthase expression. Whether activation of the AT2 receptor will have therapeutic benefit in chronic kidney disease will require further study.
authors.affiliation: Clinical Pharmacology Unit, Institute of Experimental and Clinical Toxicology and Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. benndorf@uke.uni-hamburg.de
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Benndorf
authors.forename: Christian
authors.initials: C
authors.lastname: Krebs
authors.forename: Birgit
authors.initials: B
authors.lastname: Hirsch-Hoffmann
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cieslar
authors.forename: Robin
authors.initials: R
authors.lastname: Schmidt-Haupt
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Thaiss
authors.forename: Munif
authors.initials: M
authors.lastname: Haddad
authors.forename: Susanne
authors.initials: S
authors.lastname: Fehr
authors.forename: Andreas
authors.initials: A
authors.lastname: Heilmann
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.forename: Heimo
authors.initials: H
authors.lastname: Ehmke
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Stahl
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Ulrich O
authors.initials: UO
authors.lastname: Wenzel
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D002908:Chronic Disease; D007249:Inflammation; D007668:Kidney / Q000293:injuries*; D007674:Kidney Diseases / Q000401:mortality*; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency*; D015996:Survival Rate
chemical_list: D044139:Receptor, Angiotensin, Type 2