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J Pharmacol Toxicol Methods ; 57(3): 188-93, 2008.
Article in English | MEDLINE | ID: mdl-18367412

ABSTRACT

INTRODUCTION: Animal models that closely resemble the pathophysiology of human overactive bladder are important for evaluating novel therapeutics to treat the disorder. We established a non-invasive hyperactive bladder model that is sensitive to anti-muscarinic drugs and without bladder inflammation. METHODS: Acetic acid solution was infused into the bladder for 5 min via the urethral orifice without any surgical procedures under isoflurane anaesthesia. After washing the bladder with saline, voiding frequency (VF) and total urine volume were determined for 9 h under conscious conditions. RESULTS: Infusion of a 0.5% acetic acid solution caused a significant increase in VF, without influencing total urine volume or inducing significant histopathological inflammatory alterations in the bladder urothelium. Oral administration of oxybutynin (3 and 10 mg/kg) significantly ameliorated increases in VF induced by 0.5% acetic acid. Infusion of 0.75% acetic acid induced intensive urinary inflammation and a decrease in total urine volume as well as an increase in VF. Oral treatment with oxybutynin (10 mg/kg) did not significantly improve the increased VF due to 0.75% acetic acid. Acetic acid (0.5%) infusion evoked bladder hyper-responsiveness whether applied at night or during the day. However, VF was increased more by the nighttime application of acetic acid, while there were no significant differences in basal levels of VF between daytime and nighttime. DISCUSSION: In this study, the non-invasive rat urinary hyperactive bladder model indicated minimizes the secondary effects of experimental procedures such as surgical operations and anesthesia on bladder function and is sensitive to oxybutynin. Thus, the model may be useful for investigating novel therapeutics for OAB treatment.


Subject(s)
Acetic Acid/pharmacology , Urinary Bladder, Overactive/chemically induced , Urinary Bladder/drug effects , Urination/drug effects , Urodynamics/drug effects , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Mandelic Acids/therapeutic use , Muscarinic Antagonists/therapeutic use , Rats , Rats, Sprague-Dawley , Reflex/drug effects , Time Factors , Urinary Bladder/pathology , Urinary Bladder/physiopathology , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/physiopathology
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