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. 2015 Mar;19(1):19-26.
doi: 10.5213/inj.2015.19.1.19. Epub 2015 Mar 26.

Mirodenafil prevents bladder dysfunction induced by chronic bladder ischemia in rats

Hoon Choi  1 , Jae Hyun Bae  1 , Ji Sung Shim  1 , Jae Young Park  1 , Du Geon Moon  2 , Jeong Gu Lee  3
Affiliations

Mirodenafil prevents bladder dysfunction induced by chronic bladder ischemia in rats

Hoon Choi et al. Int Neurourol J. 2015 Mar.

Abstract

Purpose: To investigate the protective effect of mirodenafil on bladder function in a rat model of chronic bladder ischemia (CBI).

Methods: Twenty-four Sprague-Dawley rats were randomized to three groups: untreated, sham-operated rats (control group); untreated, CBI model rats (CBI group); and CBI rats treated daily with 4 mg/kg mirodenafil (CBI+mirodenafil group). The CBI and CBI+mirodenafil groups underwent endothelial injury to the iliac arteries and were fed a 2% cholesterol diet after injury. Four weeks after surgery, the CBI+mirodenafil group started daily treatment with mirodenafil for four weeks. Eight weeks after surgery, continuous in vivo cystometry and in vivo organ bath studies of detrusor muscle strips were performed.

Results: in vivo cystometry revealed that the rats in the CBI group had a significantly higher micturition frequency, lower bladder capacity, and lower compliance than the rats in the control and CBI+mirodenafil groups. The detrusor muscle strip study showed that the magnitude of the carbachol-induced contractile response was significantly lower in the CBI group compared to either the control or CBI+mirodenafil group. Addition of daily mirodenafil after induction of CBI decreased the contractile response, compared to untreated CBI rats. CBI induced submucosal fibrosis and degenerative changes in bladder walls, which was reversed by the addition of mirodenafil.

Conclusions: Daily treatment with mirodenafil showed protective effects against bladder dysfunction resulting from CBI in rats.

Keywords: Ischemia; Phosphodiesterase 5 Inhibitors; Urinary Bladder.

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Conflict of interest statement

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.
Representative cystometric curves in each group. Intercontraction interval was significantly shorter in chronic bladder ischemia (CBI) rats than in the other groups. (A) Control group, (B) CBI group, and (C) CBI+mirodenafil group.
Fig. 2.
Fig. 2.
Carbachol-induced contraction in the detrusor muscle strip from the control group, chronic bladder ischemia (CBI) group, and CBI+mirodenafil group. Contractile responses induced by carbacholin the CBI group were lower than in the control and CBI+mirodenafil groups (10-6mol/L to 10-3mol/L). *Higher in control group vs. CBI group (P<0.05). †Higher in CBI group vs. CBI+mirodenafil group (P<0.05).
Fig. 3.
Fig. 3.
Bladder tissue of control group (A), chronic bladder ischemia (CBI) group (B), and CBI+mirodenafil group (C) (Masson trichrome stain, ×100).
Fig. 4.
Fig. 4.
Percentage of collagen in the muscle layer in control, chronic bladder ischemia (CBI), and CBI+mirodenafil groups. *Higher in control group vs. CBI group (P<0.05). †Higher in CBI group vs. CBI+mirodenafil group (P<0.05).
See this image and copyright information in PMC

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