Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats.
Am J Physiol Renal Physiol
; 297(2): F362-70, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19474186
ABSTRACT
Sildenafil was the first selective inhibitor of phosphodiesterase-5 (PDE5) to be widely used for treating erectile dysfunction. Many recent studies have investigated the cardioprotective role of sildenafil in animal models. We evaluated the protective effects of sildenafil in experimental renal ischemia-reperfusion (IR) injury in two studies. In study 1, male Sprague-Dawley rats were divided into four groups sham, sildenafil-treated sham, vehicle-treated IR, and sildenafil-treated IR groups. In study 2, we divided the rats into two groups sildenafil-treated IR rats and PD98059 (ERK inhibitor)+sildenafil-treated IR rats. Functional parameters of the kidney were evaluated at the molecular and structural levels. Blood urea nitrogen (BUN) and serum creatinine levels were lower in sildenafil-treated IR rats than in vehicle-treated IR rats. The expression of inducible (iNOS) and endothelial nitric oxide synthase (eNOS) proteins in sildenafil-treated IR rats was significantly higher than in vehicle-treated IR rats. Pretreatment with sildenafil in IR rats increased ERK phosphorylation and reduced the renal Bax/Bcl-2 ratio, renal caspase-3 activity, and terminal dUTP nick end-labeling-positive apoptotic cells. In contrast, PD98059 treatment increased BUN and serum creatinine levels and attenuated the sildenafil-induced expression of pERK, iNOS, eNOS, and Bcl-2. PD98059 also increased caspase-3 activity but did not decrease the sildenafil-induced accumulation of cGMP. In conclusion, this study suggests that sildenafil has antiapoptotic effects in experimental IR renal injury via ERK phosphorylation, induction of iNOS and eNOS production, and a decrease in the Bax/Bcl-2 ratio.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
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Piperazinas
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Sulfonas
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Daño por Reperfusión
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Inhibidores de Fosfodiesterasa 5
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Enfermedades Renales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2009
Tipo del documento:
Article