Korean J Urol.  2013 May;54(5):339-344. 10.4111/kju.2013.54.5.339.

Effects of Mirodenafil, a Phosphodiesterase-5 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model: Physiological and Immunohistochemical Aspects

• Kang JY
• Kim EK
• Kim KM

• KMID: 2061517
• DOI: http://doi.org/10.4111/kju.2013.54.5.339

Abstract

PURPOSE
We investigated the effects of mirodenafil, a phosphodiesterase-5 inhibitor developed in South Korea, on the female rat bladder in a partial bladder outlet obstruction (BOO) model.
MATERIALS AND METHODS
Thirty-six female Sprague-Dawley rats were divided into four groups: the control group, BOO without medication group, BOO with mirodenafil 1 mg/kg group, and BOO with mirodenafil 4 mg/kg group. Mirodenafil was administered orally for 2 weeks after the induction of BOO. Two weeks after BOO, the rats in each group underwent cystometry under urethane anesthesia. After cystometry, the bladder was excised to perform immunohistochemical staining for connexin 43.
RESULTS
The three BOO groups showed significant increases in mean bladder weight compared with the control group. Baseline pressure, threshold pressure, and maximum contraction pressure were not significantly different between the four groups. Although the contraction interval was decreased in all BOO groups compared with the control group, it was prolonged in the two groups treated with mirodenafil compared with the untreated BOO group. In the immunohistochemical examination, connexin 43 staining intensity in the lamina propria increased in the three BOO groups compared with the control group. The two groups treated with mirodenafil, however, showed decreased connexin 43 staining compared with the untreated BOO group.
CONCLUSIONS
Mirodenafil may increase the contraction intervals of female rat bladders in a partial BOO model. Decreasing bladder overactivity by mirodenafil may be related to intracellular communication mechanisms involving connexin 43.

Keyword

Connexin 43; Overactive urinary bladder; Phosphodiesterase inhibitors; Urinary bladder neck obstruction

MeSH Terms

Anesthesia
Animals
Connexin 43
Contracts
Cyclic Nucleotide Phosphodiesterases, Type 5
Female
Humans
Mucous Membrane
Phosphodiesterase Inhibitors
Pyrimidinones
Rats
Rats, Sprague-Dawley
Republic of Korea
Sulfonamides
Urethane
Urinary Bladder
Urinary Bladder Neck Obstruction
Urinary Bladder, Overactive
Connexin 43
Cyclic Nucleotide Phosphodiesterases, Type 5
Phosphodiesterase Inhibitors
Pyrimidinones
Sulfonamides
Urethane

Figure

• 

  FIG. 1 Representative photograph of hematoxylin and eosin staining of each group (×40). Bladder wall thickness of the 3 bladder outlet obstruction (BOO) groups increased compared with that of the control group. (A) Control group, (B) BOO without medication group, (C) BOO with 1 mg/kg mirodenafil group, and (D) BOO with 4 mg/kg mirodenafil group.

• 

  FIG. 2 Representative photograph of immunohistochemical staining for connexin 43 in each group (×100). Connexin 43 was mainly localized in the lamina propria (arrow). Staining intensity increased in the three bladder outlet obstruction (BOO) groups compared with the control group, but was decreased in the two groups treated with mirodenafil compared with the untreated BOO group. (A) Control group, (B) BOO without medication group, (C) BOO with 1 mg/kg mirodenafil group, and (D) BOO with 4 mg/kg mirodenafil group.

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