Korean J Urol.  2007 Aug;48(8):832-837. 10.4111/kju.2007.48.8.832.

Effects of Rho Kinase Inhibitor on Detrusor Overactivity after Bladder Outlet Obstruction in Rats

• Kim HW
• Cho SY
• Park DJ
• Yoon BI
• Lee JY

• KMID: 2061277
• DOI: http://doi.org/10.4111/kju.2007.48.8.832

Abstract

PURPOSE
A partial bladder outlet obstruction(PBOO) related detrusor hypertrophy is associated with up-regulation of the Rho kinase activity in an experimental animal model, and has been implicated in PBOO induced bladder dysfunction. The effect of a Rho kinase inhibitor on the voiding function in anesthetized rats with PBOO was investigated.
MATERIALS AND METHODS
Eighteen Sprague-Dawley rats were divided into control(9 rats) and experimental(9 rats) groups. The experimental group was partially obstructed for 6 weeks, with cystometrograms(CMG) then were performed. The number of voids, and the intercontraction interval (ICI) and peak pressure(PP) were recorded. Rho kinase inhibitors were administered to the experimental group. An additional CMG was performed to observe the effects of Rho kinase inhibition. Bladder tissues were immunohistochemically(IHC) evaluated for the expression of RhoA protein.
RESULTS
The bladder weights of the PBOO group were significantly increased compared with the control group(p<0.05). Significant increases in the voiding frequency and PP, but a significant decrease in the ICI was observed in the PBOO group compared to the control group on the CMG (p<0.05). The voiding frequency of the PBOO group was significantly decreased after Rho kinase inhibitor treatment(p<0.05). The Rho kinase inhibitor treated group showed a decrease in the PP and an increase in the ICI compared to the PBOO group. The IHC showed a higher RhoA protein expression in the bladder tissues of the PBOO group.
CONCLUSIONS
H-1152, a specific inhibitor of Rho kinase, attenuates the PBOO-related detrusor overactivity in a rat model. The Rho kinase inhibitor appears to be a novel strategy for the management of bladder overactivity.

Keyword

Urinary bladder neck obstruction; Rho-associated kinase; Rats

MeSH Terms

Animals
Hypertrophy
Models, Animal
Rats*
Rats, Sprague-Dawley
rho-Associated Kinases*
rhoA GTP-Binding Protein
Up-Regulation
Urinary Bladder Neck Obstruction*
Urinary Bladder*
Weights and Measures
rho-Associated Kinases
rhoA GTP-Binding Protein

Figure

• 

  Fig. 1 Changes of the voiding frequency in the control (n=9); partial bladder outlet obstruction (PBOO, n=9) and Rho kinase inhibitor treated (PBOO after RKI, n=9) groups. The data are expressed as the means±SEM. *: p<0.05 compared to the control group, † : p<0.05 compared to the PBOO group.

• 

  Fig. 2 Changes of the peak pressure in the control (n=9), partial bladder outlet obstruction (PBOO, n=9) and Rho kinase inhibitor treated (PBOO after RKI, n=9) groups. The data are expressed as the means±SEM. *: p<0.05 compared to the control group.

• 

  Fig. 3 Changes of the intercontraction interval (ICI) in the control (n=9), partial bladder outlet obstruction (PBOO, n=9) and Rho kinase inhibitor treated (PBOO after RKI, n=9) groups. The data are expressed as the means±SEM. *: p<0.05 compared to the control group.

• 

  Fig. 4 Representative photomicrograph showing immunolocalization of RhoA proteins in the bladder tissue from the control (A) and partial bladder outlet obstruction (B) groups (×20). Immunolocalization was observed predominantly in the detrusor smooth muscle areas, but to a lesser extentin the urothelial layer. Arrows indicate densely immunostained areas. Image analysis showing an increased intensity of the reaction products in the bladder tissue section of the partial bladder outlet obstruction group.

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