Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice.
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Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice. / Benndorf, Ralf; Krebs, Christian; Hirsch-Hoffmann, Birgit; Schwedhelm, Edzard; Cieslar, Gabriele; Schmidt-Haupt, Robin; Steinmetz, Oliver; Meyer-Schwesinger, Catherine; Thaiss, Friedrich; Haddad, Munif; Fehr, Susanne; Heilmann, Andreas; Helmchen, Udo; Hein, Lutz; Ehmke, Heimo; Stahl, Rolf A.K.; Böger, Rainer; Wenzel, Ulrich.
In: KIDNEY INT, Vol. 75, No. 10, 10, 2009, p. 1039-1049.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Angiotensin II type 2 receptor deficiency aggravates renal injury and reduces survival in chronic kidney disease in mice.
AU - Benndorf, Ralf
AU - Krebs, Christian
AU - Hirsch-Hoffmann, Birgit
AU - Schwedhelm, Edzard
AU - Cieslar, Gabriele
AU - Schmidt-Haupt, Robin
AU - Steinmetz, Oliver
AU - Meyer-Schwesinger, Catherine
AU - Thaiss, Friedrich
AU - Haddad, Munif
AU - Fehr, Susanne
AU - Heilmann, Andreas
AU - Helmchen, Udo
AU - Hein, Lutz
AU - Ehmke, Heimo
AU - Stahl, Rolf A.K.
AU - Böger, Rainer
AU - Wenzel, Ulrich
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 75
SP - 1039
EP - 1049
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 10
M1 - 10
ER -
