Ann Rehabil Med.  2014 Aug;38(4):433-442. 10.5535/arm.2014.38.4.433.

Effects of Bladder Function by Early Tamsulosin Treatment in a Spinal Cord Injury Rat Model

• Lee KK
• Lee MY
• Han DY
• Jung HJ
• Joo MC

• KMID: 2165725
• DOI: http://doi.org/10.5535/arm.2014.38.4.433

Abstract

OBJECTIVE
To investigate the effects of early tamsulosin treatment on changes in bladder characteristics after a spinal cord injury.
METHODS
We divided 45 rats into three groups: the control (CON) group, the spinal cord injury (SCI) group, and the SCI+tamsulosin treatment (SCI+TAM) group. Spinal cord transection was performed in the SCI and SCI+TAM groups. Tamsulosin was injected for 7 days in the SCI+TAM group. Intravesical and intra-abdominal catheters were implanted before cord injury. Basal pressure (BP), maximal vesical pressure (MVP), micturition volume (MV), and voiding interval time (VIT) were measured at 7 days after SCI. The bladder was then removed and used for an in vitro organ bath study and Western blot analysis. The percentage changes in contractility from baseline after acetylcholine alone, pretreatment with a muscarinic 2 (M2) receptor blocker (AQ-RA741), and pretreatment with a M3 receptor blocker (4-DAMP) were compared among the groups. Western blot analyses were performed to determine expression levels of pERK1/2 and rho-kinase.
RESULTS
In cystometry, MVP, BP, MV, and VIT showed changes in the SCI and SCI+TAM groups versus the CON group (p<0.05). In the organ bath study, acetylcholine-induced contractility in the three groups differed significantly (p<0.05). Additionally, acetylcholine-induced contractility with 4-DAMP pretreatment was reduced significantly in the SCI+TAM group versus the SCI group. In Western blotting, pERK1/2 expression was stronger (p<0.05) and rho-kinase expression was weaker in the SCI+TAM group than the SCI group (p<0.05).
CONCLUSION
These results suggest that the bladder contraction due to acetylcholine after SCI can be decreased by tamsulosin in the acute stage and this involves changes in pERK1/2 and rho-kinase.

Keyword

Spinal cord injuries; Tamsulosin; Neurogenic urinary bladder

MeSH Terms

Acetylcholine
Animals
Baths
Blotting, Western
Catheters
Models, Animal*
Rats
rho-Associated Kinases
Spinal Cord Injuries*
Urinary Bladder*
Urinary Bladder, Neurogenic
Urination
Acetylcholine
rho-Associated Kinases

Figure

• 

  Fig. 1 Percentage changes in contractility for the CON, SCI, and SCI+TAM groups. The intergroup difference in the percentage changes in contractility was significant. The values are expressed as mean±standard deviation. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the CON group and the others (p<0.05). †Denotes significant difference between the SCI group and the SCI+TAM group (p<0.05).

• 

  Fig. 2 Percentage changes in contractility after pretreatment with M2 receptor antagonist (AQ-RA) for the CON, SCI, and SCI+TAM groups. The intergroup difference in the percentage changes in contractility was not significant. The values are expressed as mean±standard deviation. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the CON group and the others (p<0.05).

• 

  Fig. 3 Percentage changes in contractility after pretreatment with M3 receptor antagonist (4-DAMP) for the CON, SCI, and SCI+TAM groups. The intergroup difference in the percentage changes in contractility was significant. The values are expressed as mean±standard deviation. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the CON group and the others (p<0.05). †Denotes significant difference between the SCI group and the SCI+TAM group (p<0.05).

• 

  Fig. 4 Results of awake cystometry. In the control, increases in the pressure of the bladder and urinary voiding time shown a matching pattern. However, the SCI and SCI+TAM groups did not match. The SCI group has a more frequent voiding pattern. CON, control; SCI, spinal injury-induced; TAM, tamsulosin.

• 

  Fig. 5 Basal pressure (BP, A) and maximal vesical pressure (MVP, B) of the CON, SCI, and SCI+TAM groups; there are significant difference between the CON group and the others. However, there was no significant difference between the SCI and SCI+TAM groups. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the CON group and the others (p<0.05).

• 

  Fig. 6 Micturition volume (MV, A) and voiding interval time (VIT, B) of the CON, SCI, and SCI+TAM groups; there are significant difference between the CON group and the others. However, there was no significant difference between the SCI and the SCI+TAM groups. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the CON group and the others (p<0.05).

• 

  Fig. 7 Results of Western blot analysis for extracellular signal-regulated kinases 1/2 (ERK1/2, B), phosphorylated ERK1/2 (pERK1/2, C), and rho-kinase (D) in the bladder. (A) shows representative cases for each protein. Note the prominent expression of pERK1/2 and lower expression of rho-kinase in the SCI+TAM group than in the SCI group. (B), (C), and (D) showed the optical density analysis for ERK1/2, pERK1/2, and rho-kinase. CON, control; SCI, spinal injury-induced; TAM, tamsulosin. *Denotes significant difference between the SCI group and the others (p<0.05).

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