Therapeutic potential of muscle growth promoters in a stress urinary incontinence model.
Am J Physiol Renal Physiol
; 319(3): F436-F446, 2020 09 01.
Article
en En
| MEDLINE
| ID: mdl-32686522
ABSTRACT
Weakness of urinary sphincter and pelvic floor muscles can cause insufficient urethral closure and lead to stress urinary incontinence. Bimagrumab is a novel myostatin inhibitor that blocks activin type II receptors, inducing skeletal muscle hypertrophy and attenuating muscle weakness. ß2-Adrenergic agonists, such as 5-hydroxybenzothiazolone derivative (5-HOB) and clenbuterol, can enhance muscle growth. We hypothesized that promoting muscle growth would increase leak point pressure (LPP) by facilitating muscle recovery in a dual-injury (DI) stress urinary incontinence model. Rats underwent pudendal nerve crush (PNC) followed by vaginal distension (VD). One week after injury, each rat began subcutaneous (0.3 mL/rat) treatment daily in a blinded fashion with either bimagrumab (DI + Bim), clenbuterol (DI + Clen), 5-HOB (DI + 5-HOB), or PBS (DI + PBS). Sham-injured rats underwent sham PNC + VD and received PBS (sham + PBS). After 2 wk of treatment, rats were anesthetized for LPP and external urethral sphincter electromyography recordings. Hindlimb skeletal muscles and pelvic floor muscles were dissected and stained. At the end of 2 wk of treatment, all three treatment groups had a significant increase in body weight and individual muscle weight compared with both sham-treated and sham-injured rats. LPP in DI + Bim rats was significantly higher than LPP of DI + PBS and DI + Clen rats. There were more consistent urethral striated muscle fibers, elastin fibers in the urethra, and pelvic muscle recovery in DI + Bim rats compared with DI + PBS rats. In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured external urethral sphincter and pelvic floor muscle recovery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Incontinencia Urinaria
/
Incontinencia Urinaria de Esfuerzo
/
Clenbuterol
/
Anticuerpos Monoclonales Humanizados
Límite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Asunto de la revista:
FISIOLOGIA
/
NEFROLOGIA
Año:
2020
Tipo del documento:
Article