Angiotensin converting enzyme inhibitor but not angiotensin receptor blockade or statin ameliorates murine adriamycin nephropathy.
Kidney Int
; 73(3): 288-99, 2008 Feb.
Article
em En
| MEDLINE
| ID: mdl-18033243
ABSTRACT
Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins have renoprotective effects. We studied the cellular mechanisms for this effect in adriamycin-treated mice receiving captopril, losartan, simvastatin, or their combinations. The mice developed albuminuria, renal insufficiency, and parenchymal inflammation/fibrosis accompanied by overexpression of intrarenal converting enzyme and angiotensin II. Only captopril consistently improved these abnormalities and reduced the cortical expression of several proinflammatory and profibrotic factors including transforming growth factor-beta (TGF-beta). These effects were independent of blood pressure, accompanied by increased urine N-acetylseryl-aspartyl-lysyl-proline (Ac-SDKP) levels, and the restoration of renal angiotensin-converting enzyme and angiotensin II to baseline levels. Losartan or simvastatin alone or together had no effect, and their addition to captopril did not enhance protection. In vitro, angiotensin II stimulated TGF-beta in renal tubular cells via mitogen-activated protein kinase (MAPK) signaling. Captopril or Ac-SDKP suppressed angiotensin II-induced MAPK activation and TGF-beta secretion. Angiotensin-converting enzyme inhibition confers renoprotection in adriamycin nephropathy by reducing intrarenal angiotensin II and augmenting Ac-SDKP expression that together attenuate MAPK signaling and its downstream proinflammatory and fibrogenic properties. The addition of receptor blocker and/or statin failed to potentiate such effects.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Enzima Conversora de Angiotensina
/
Glomerulosclerose Segmentar e Focal
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
Bloqueadores do Receptor Tipo 1 de Angiotensina II
/
Rim
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
China