Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK.
J Sex Med
; 11(9): 2164-71, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-24919622
ABSTRACT
INTRODUCTION:
The pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known.AIMS:
The aim of this study was to determine whether hydroxyl fasudil, a ROCK inhibitor, affects diabetic neuropathy-related ED.METHODS:
Type 1 diabetes mellitus was induced in male rats by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic rats were administered hydroxyl fasudil, a selective ROCK inhibitor (10 mg/kg/day, intraperitoneally) or vehicle, for 4 weeks. Age-matched control, nondiabetic, rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a 2 day washout, neuro-stimulated erectile function was evaluated. Major pelvic ganglia (MPG) were collected for Western blot analysis of RhoA, ROCK-1, ROCK-2, phospho (P)-AKT (Ser(473) ), and P-phosphatase and tensin homolog (P-PTEN) (Ser(380) /Thr(382/383) ). MAIN OUTCOMEMEASURES:
Effect of ROCK inhibitor hydroxyl fasudil on erectile function and ROCK/P-AKT/P-PTEN pathway in the MPG of diabetic rats.RESULTS:
Erectile response was significantly (P < 0.05) reduced in diabetic rats compared with nondiabetic rats and was preserved (P < 0.05) in diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK-2 protein expressions in MPG were increased (P < 0.05) and remained increased in hydroxyl fasudil-treated rats. P-AKT (Ser(473) ) expression was decreased (P < 0.05), whereas P-PTEN (Ser(380) /Thr(382/383) ) expression was increased (P < 0.05) in MPG of diabetic rats compared with nondiabetic rats, and both were reversed (P < 0.05) in diabetic rats treated with hydroxyl fasudil.CONCLUSION:
Improved erectile function and restored P-AKT and P-PTEN in the MPG with hydroxyl fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in neurogenic diabetic ED.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Erección Peniana
/
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina
/
Proteína de Unión al GTP rhoA
/
Inhibidores de Proteínas Quinasas
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Diabetes Mellitus Experimental
/
Quinasas Asociadas a rho
Límite:
Animals
Idioma:
En
Revista:
J Sex Med
Asunto de la revista:
GINECOLOGIA
/
MEDICINA REPRODUTIVA
/
UROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos