Aldosterone mediates glomerular inflammation in experimental mesangial proliferative glomerulonephritis.
BACKGROUND
The renoprotection of the mineralocorticoid receptor antagonist (MRA) is considered to be mainly via its antifibrotic activity, and the possibility that it may also have antiinflammatory effects has not been studied. We tested the hypothesis that MRA might influence the inflammatory changes that accompany experimental glomerular injury.


METHODS
Administration of vehicle (control) or a selective MRA, eplerenone (50 mg/kg x 2 times/day) was started 7 days (-7d) before induction of anti-Thy-1.1 glomerulonephritis. Kidney samples were evaluated serially over a 12-day period for the presence of cell proliferation, macrophage infiltration, mesangial cell phenotypic activation and expression of the chemokine monocyte chemoattractant protein-1 (MCP-1).


RESULTS
MRA did not prevent the mesangiolysis associated with anti-Thy-1 antibody. However, MRA significantly inhibited MCP-1 expression, glomerular macrophage infiltration and mesangial phenotypic activation (alpha-smooth muscle actin expression).


CONCLUSIONS
MRA alters glomerular inflammation and mesangial cell activation in experimental glomerular injury. MRA may be a novel way to treat acute glomerular diseases.
Division of Nephrology, Department of Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Danping
D
Qin
Hiroyuki
H
Morita
Kiyoko
K
Inui
Hironori
H
Tayama
Yoshihiko
Y
Inoue
Ashio
A
Yoshimura
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D000077545:Eplerenone; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007518:Isoantibodies; D008264:Macrophages; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000199:Actins; D000450:Aldosterone; D018932:Chemokine CCL2; D003404:Creatinine; D003849:Deoxyguanosine; D000077545:Eplerenone; D007518:Isoantibodies; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; C035678:anti-Thy antibody; C498862:Acta2 protein, rat