Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor
| Autor: | Hiromi Kumon, Naoki Yoshimura, Jun Nishiguchi, Peter B. Snyder, Michael B. Chancellor, Dong Deuk Kwon, Yasuhiro Kaiho |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Phosphodiesterase Inhibitors Urology medicine.medical_treatment urologic and male genital diseases Rats Sprague-Dawley Bladder outlet obstruction Internal medicine medicine Animals Phosphodiesterase inhibitor Ligature biology medicine.diagnostic_test Urinary Bladder Overactive business.industry Cystometry Muscle Smooth medicine.disease female genital diseases and pregnancy complications Cyclic Nucleotide Phosphodiesterases Type 4 Rats Urinary Bladder Neck Obstruction Endocrinology Blood pressure Urethra medicine.anatomical_structure Overactive bladder 3' 5'-Cyclic-AMP Phosphodiesterases Enzyme inhibitor biology.protein Female business Muscle Contraction |
| Zdroj: | BJU International. 99:680-686 |
| ISSN: | 1464-410X 1464-4096 |
| DOI: | 10.1111/j.1464-410x.2006.06643.x |
| Popis: | OBJECTIVE To investigate the effects of a selective type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, IC486051, on bladder activity in normal rats and those with and bladder outlet obstruction (BOO), as inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation of smooth muscle. MATERIALS AND METHODS BOO was induced in female Sprague-Dawley rats by tying a silk ligature around the urethra. At 4 or 6 weeks after inducing BOO, conscious rats were assessed by cystometry with the urethral ligature intact. In unobstructed rats, blood pressure was also measured. RESULTS In unobstructed rats, IC486051 (0.1 mg/kg intravenously) produced no significant changes in cystometric variables, while at a dose of 0.5 mg/kg maximum voiding pressure was reduced by 34%. At both doses, there was a small, transient increase in blood pressure. In both 4- and 6-week BOO rats IC486051 dose-dependently decreased the number and amplitude of non-voiding bladder contractions by up to 80%, relative to pre-treatment values. At doses of 0.1 and 0.5 mg/kg IC486051 had no significant effect on voiding variables. In the 4-week BOO rats, a dose of 1.0 mg/kg decreased bladder capacity, voided volume and residual volume by 21%, 32% and 18%, respectively. In 6-week BOO rats, a dose of 1.0 mg/kg decreased maximal voiding pressure by 17% and pressure threshold for voiding by 28%. In both groups of rats with BOO, voiding efficiency was unchanged. CONCLUSIONS A selective PDE4 inhibitor can effectively suppress detrusor overactivity in rats with BOO, at doses that have no effect on voiding bladder contractions. Thus, selective PDE4 inhibitors should be considered for the treatment of overactive bladder in patients with BOO. |
| Databáze: | OpenAIRE |
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