Arterial wall hypertrophy is ameliorated by α2-adrenergic receptor antagonist or aliskiren in kidneys of angiotensinogen-knockout mice.
Clin Exp Nephrol
; 22(4): 773-781, 2018 Aug.
Article
em En
| MEDLINE
| ID: mdl-29230587
ABSTRACT
BACKGROUND:
Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg -/-) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-ß1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-ß1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required.METHODS:
We performed renal denervation and administered the α2-adrenergic receptor (AR) antagonist, atipamezole, to Atg -/- mice. A renin inhibitor, aliskiren, which was preliminarily confirmed to reduce TGF-ß1 gene expression in kidneys of the mice, was additionally administered to assess the effect on the arterial hypertrophy and interstitial fibrosis.RESULTS:
Norepinephrine content in kidneys of Atg -/- mice was three times higher than in kidneys of wild-type mice. Interventions by renal denervation and atipamezole resulted in amelioration of the histological findings. Overexpression of TGF-ß1 gene in kidneys of Atg -/- mice was altered in a manner linked to the histological findings. Surprisingly, aliskiren reduced α2-AR gene expression, interstitial fibrosis, and arterial hypertrophy in kidneys of Atg -/- mice, which lack renin substrate.CONCLUSIONS:
Alpha2-AR signaling is one of the causes of persistent renal arterial hypertrophy in Atg -/- mice. Aliskiren also angiotensinogen-independently reduces the extent of renal arterial hypertrophy, partly thorough downregulation of α2-ARs. Although renal arterial hypertrophy in Atg -/- mice appears to be of multifactorial origin, TGF-ß1 may play a key role in the persistence of such hypertrophy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Renal
/
Antagonistas de Receptores Adrenérgicos alfa 2
/
Fumaratos
/
Amidas
Limite:
Animals
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Exp Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão