Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.
Clin Exp Nephrol
; 23(4): 455-464, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30426292
ABSTRACT
BACKGROUND:
Tolvaptan is an effective treatment for polycystic kidney disease (PKD), but also causes unfortunate polyuria. Hydrochlorothiazide (HCTZ) has been shown to reduce urine volume in nephrogenic diabetes insipidus, raising the possibility that HCTZ could also be effective in reducing tolvaptan-induced polyuria. In this study, we examined the combined administration of HCTZ and tolvaptan.METHODS:
Male PCK rats were divided into four groups of normal chow (Cont), normal chow plus tolvaptan, gavage HCTZ treatment, and tolvaptan + HCTZ. Biochemical examinations of the plasma and urine were performed as well as histological and molecular (mRNA and protein expression) analyses.RESULTS:
Groups treated with tolvaptan had significantly higher 24 h urine excretion, which was significantly reduced in the tolvaptan + HCTZ group after 2 weeks. Cyst size, pERK protein expression, and Cyclin D1 mRNA expression were all significantly reduced in both the tolvaptan and tolvaptan + HCTZ groups, indicating that HCTZ did not affect the beneficial functions of tolvaptan. Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group. The renal glomerular filtration rate was reduced in the tolvaptan + HCTZ group. Significantly lowered mRNA expression of neuronal nitric oxide synthase, prostaglandin E synthase 2 and renin were also found in the medulla, but not in the cortex.CONCLUSION:
HCTZ reduces tolvaptan-induced polyuria without altering its beneficial effects on PKD. This novel therapeutic combination could potentially lead to better PKD treatments and improved quality of life for the affected patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliúria
/
Diuréticos
/
Antagonistas dos Receptores de Hormônios Antidiuréticos
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Tolvaptan
/
Hidroclorotiazida
/
Doenças Renais Policísticas
Limite:
Animals
Idioma:
En
Revista:
Clin Exp Nephrol
Assunto da revista:
NEFROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão