Noritoshi Sekido1, Jun Kida2, Daisuke Wakamatsu2, Hiroki Okada2, Hidekazu Matsuya2. 1. Department of Urology, Toho University Medical Center Ohashi Hospital, Meguro-ku, Tokyo, Japan. Electronic address: nsekido@med.toho-u.ac.jp. 2. Group2 Discovery Research Laboratories, Ono Pharmaceutical Co, Ltd, Mishima-gun, Osaka, Japan.
Abstract
OBJECTIVE: To examine the lower urinary tract function of a rat lumbar canal stenosis (LCS) model by in vivo cystometry before and after α1 adrenoceptor antagonist or cholinesterase inhibitor administration. MATERIALS AND METHODS: One small hole was drilled at the fifth lumbar vertebral arch, and a rectangular piece of silicone rubber was inserted into the L5-L6 epidural space. Two weeks after the surgery, awake cystometry was performed before and after the oral administration of the vehicle, tamsulosin (TAM, 0.03 and 0.1 mg/kg), or distigmine (DIS, 0.3 and 1 mg/kg). We compared the awake cystometry parameters before and after drug administration. RESULTS: The LCS rats showed a large maximum cystometric capacity (MCC) and a high residual urine rate with a lower maximum bladder pressure during micturition (Pmax). TAM and DIS significantly decreased the pressure at the onset of voiding contraction, MCC, and postvoid residual urine volume. Residual urine rate was also significantly decreased by DIS at 0.3 and 1.0 mg/kg, and TAM at 0.03 mg/kg. DIS significantly increased the frequency of nonvoiding contractions per minute. Pmax was not significantly different even after administration of DIS. CONCLUSION: The LCS rats had salient characteristics of severe infra-sacral neuropathic bladder dysfunction. TAM and DIS decreased postvoid residual urine volume, but this decrease was not accompanied by an increased Pmax or increased voided volume. Rather, decreased MCC was a possible contributing factor. Moreover, increased nonvoiding contractions after administration of DIS might participate in the decreased MCC. This novel model will be useful in studying the pharmacotherapy of the underactive bladder.
OBJECTIVE: To examine the lower urinary tract function of a rat lumbar canal stenosis (LCS) model by in vivo cystometry before and after α1 adrenoceptor antagonist or cholinesterase inhibitor administration. MATERIALS AND METHODS: One small hole was drilled at the fifth lumbar vertebral arch, and a rectangular piece of silicone rubber was inserted into the L5-L6 epidural space. Two weeks after the surgery, awake cystometry was performed before and after the oral administration of the vehicle, tamsulosin (TAM, 0.03 and 0.1 mg/kg), or distigmine (DIS, 0.3 and 1 mg/kg). We compared the awake cystometry parameters before and after drug administration. RESULTS: The LCS rats showed a large maximum cystometric capacity (MCC) and a high residual urine rate with a lower maximum bladder pressure during micturition (Pmax). TAM and DIS significantly decreased the pressure at the onset of voiding contraction, MCC, and postvoid residual urine volume. Residual urine rate was also significantly decreased by DIS at 0.3 and 1.0 mg/kg, and TAM at 0.03 mg/kg. DIS significantly increased the frequency of nonvoiding contractions per minute. Pmax was not significantly different even after administration of DIS. CONCLUSION: The LCS rats had salient characteristics of severe infra-sacral neuropathic bladder dysfunction. TAM and DIS decreased postvoid residual urine volume, but this decrease was not accompanied by an increased Pmax or increased voided volume. Rather, decreased MCC was a possible contributing factor. Moreover, increased nonvoiding contractions after administration of DIS might participate in the decreased MCC. This novel model will be useful in studying the pharmacotherapy of the underactive bladder.