Characteristics of detrusor overactivity induced by intravesical instillation of adenosine 5′-triphosphate

Abstract

Purpose: The bladder urothelium releases adenosine 5′-triphosphate (ATP) with mechanical stretch, which increases in a pathologic state such as a neurogenic bladder. We investigated the characteristics of detrusor overactivity induced by the intravesical instillation of ATP. Materials and Methods: Under urethane anesthesia, cystometry was performed on female Sprague-Dawley rats. After pretreatment with protamine sulfate (PS, 10mg/ml), ATP (60mM, pH 6.0) was continuously infused intravesically. The effects of intravenous injection of pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS) on ATP-induced detrusor overactivity were studied. Changes in cystometric parameters including parameters of each voiding phase, including bladder pressure increase rate (slope; Ph1slope), maximal bladder pressure (Ph1MBP, Ph2MBP, Ph3MBP), mean bladder pressure (Ph2meanBP) and variation of intraluminal pressure high-frequency oscillations (IPHFOs) were analysed. Results: With the intravesical instillation of ATP after PS pretreatment, the intercontraction interval (ICI) decreased significantly (544.2±167.2s vs 222.3±170.8s, p=0.001), maximal voiding pressure (MVP) decreased significantly (31.3±4.7cmH2O vs 25±2.9cmH2O, p=0.001), and pressure threshold (PT) decreased significantly (4.0±1.3cmH2O vs 1.4±0.8cmH2O, P=0.001). Changes in the ICI, MVP & PT induced by intravesical instillation of ATP were reversed by intravenous injection of PPADS. Ph1slope, Ph1MBP, Ph2MBP, Ph2meanBP and Ph3MBP were decreased, but IPHFOs were not affected by intravesical application of ATP. Conclusions: Intravesical instillation of ATP in female rats induced detrusor overactivity, which may be mediated by acting on the urine storage phase.