Int Neurourol J.  2012 Mar;16(1):13-22.

Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder

• Kim SE
• Shin MS
• Kim CJ
• Park JH
• Chung KJ
• Jung H
• Kim KH
• Lee JH
• Ko IG

Abstract

PURPOSE
The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, alpha1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats.
METHODS
Adult female Sprague-Dawley rats, weighing 250+/-10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted.
RESULTS
Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment.
CONCLUSIONS
Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.

Keyword

Overactive bladder; Cyclophosphamide; Tamsulosin; Rats

MeSH Terms

Adult
Animals
Blood-Brain Barrier
Blotting, Western
Contracts
Cyclophosphamide
Female
Humans
Immunohistochemistry
Injections, Intraperitoneal
NAD
Neurons
Nitric Oxide Synthase
Nocturia
Prostatic Hyperplasia
Rats
Rats, Sprague-Dawley
Sulfonamides
Urinary Bladder
Urinary Bladder, Overactive
Cyclophosphamide
NAD
Nitric Oxide Synthase
Sulfonamides