Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice.
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.
Benndorf
Ralf A
RA
Clinical Pharmacology Unit, Institute of Experimental and Clinical Toxicology and Pharmacology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. benndorf@uke.uni-hamburg.de
Krebs
Christian
C
Hirsch-Hoffmann
Birgit
B
Schwedhelm
Edzard
E
Cieslar
Gabriele
G
Schmidt-Haupt
Robin
R
Steinmetz
Oliver M
OM
Meyer-Schwesinger
Catherine
C
Thaiss
Friedrich
F
Haddad
Munif
M
Fehr
Susanne
S
Heilmann
Andreas
A
Helmchen
Udo
U
Hein
Lutz
L
Ehmke
Heimo
H
Stahl
Rolf A
RA
Böger
Rainer H
RH
Wenzel
Ulrich O
UO
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
D044139:Receptor, Angiotensin, Type 2