A Novel Aldosterone Antagonist Limits Renal Injury in 5/6 Nephrectomy.
Sci Rep
; 7(1): 7899, 2017 08 11.
Article
em En
| MEDLINE
| ID: mdl-28801620
ABSTRACT
Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day. A group of untreated sham-operated rats was also studied. Ly markedly raised plasma renin activity (PRA) and aldosterone, and exerted more effective anti-albuminuric and renoprotective action than eplerenone. In Protocol 2, Nx rats remained untreated until Day 60, when they were divided into Nx+V receiving vehicle; Nx+L treated with losartan, 50 mg/kg/day; Nx+L+Eple, given losartan and eplerenone, and Nx+L+Ly, given losartan and Ly. Treatments lasted for 90 days. As an add-on to losartan, Ly normalized blood pressure and albuminuria, and prevented CKD progression more effectively than eplerenone. This effect was associated with strong stimulation of PRA and aldosterone. Despite exhibiting higher affinity for the MR than either eplerenone or spironolactone, Ly caused no hyperkalemia. Ly may become a novel asset in the effort to detain the progression of CKD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antagonistas de Receptores de Mineralocorticoides
/
Insuficiência Renal Crônica
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Brasil