Co-inhibition of Angiotensin II Receptor and Endothelin-1 Attenuates Renal Injury in Unilateral Ureteral Obstructed Mice.
Kidney Blood Press Res
; 41(4): 450-9, 2016.
Article
em En
| MEDLINE
| ID: mdl-27415782
ABSTRACT
BACKGROUND/AIMS:
Both endothelin-1 (ET-1) and the renin-angiotensin system (RAS) may play important roles in renal fibrosis in the obstructed kidney. However, there have been few clear demonstrations of a relationship between their activation and additive or synergistic roles in renal fibrosis. We investigated the protective roles and relationship between renal RAS and ET-1 in unilateral ureteral obstruction (UUO) mice.METHODS:
8-week-old male C57BL/6 mice were divided into seven groups sham, bosentan+sham, valsartan+sham, vehicle+UUO, bosentan+UUO, valsartan+UUO, and valsartan+bosentan+UUO. Valsartan and bosentan were administered orally using an NG tube (valsartan 10 mg/kg/day, bosentan 100 mg/kg/day for 8 days, after which the molecular and structural kidney parameters were evaluated. Bosentan treatment elevated plasma renin activity, renal renin, and AT1R expression in UUO mice.RESULTS:
Although valsartan decreased plasma ET-1 in these mice, it did not affect ET(A) or ET(B) in their kidneys. Co-treatment with valsartan and bosentan decreased ET-1 in these mice compared to the single treatments. Bosentan, but not valsartan, elevated eNOS expression in their kidneys. Co-treatment with valsartan and bosentan reduced TGF-ß, α-SMA, and collagen IV expression, and the Masson's trichrome stained area in their kidneys.CONCLUSIONS:
Bosentan and valsartan acted complementarily, and co-treatment with both drugs had an additive protective effect against renal fibrosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Obstrução Ureteral
/
Receptores de Angiotensina
/
Endotelina-1
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Valsartana
/
Cirrose Hepática
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article