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Kim, Mon, Choi, and Kim: Characteristics of Detrusor Overactivity Induced by Intravesical Instillation of Adenosine 5'-Triphosphate
Original Article
Korean Journal of Urology

Korean Journal of Urology 2008; 49(5): 424-431.

Published online: 31 May 2008

DOI: https://doi.org/10.4111/kju.2008.49.5.424

Characteristics of Detrusor Overactivity Induced by Intravesical Instillation of Adenosine 5'-Triphosphate

Sang Jin Kim, Hong Sang Mon, Hong Yong Choi, Yong Tae Kim

Department of Urology, College of Medicine, Hanyang University, Seoul, Korea.

ytkimuro@hanyang.ac.kr

Received 15 February 2008       Accepted 7 April 2008

Copyright © 2008 The Korean Urological Association

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 pyridoxalphosphate-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.

Keywords: Rats, Detrusor overactivity, Adenosine triphosphate, Bladder

Figures and Tables

Fig. 1
An illustration of connection of experimental instruments, which consist of polyethylene-50 catheter, pressure transducer, computer, syringe pump & three-way stopcock catheter, and position of IV catheter.
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Fig. 2
Representative micturition cycle showing the phases of bladder pressure wave; micturition were divided by four phases.
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Fig. 3
Typical cystometric findings. (A) Control CMG, (B) CMG during PS instillation, (C) CMG during ATP instillation with PS pretreatment, (D) CMG after intravenous injection of PPADS (10mg/kg) during ATP instillation with PS pretreatment. CMG: cystometrography, PS: protamine sulfate, ATP: adenosine 5'-triphosphate, PPADS: pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid.
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Fig. 4
Dose-dependent changes in ICI with intravenous injection of PPADS on detrusor overactivity induced by intravesical instillation of ATP with protamine pretreatment. With the intravesical instillation of ATP after PS pretreatment, ICI was decreased significantly (*: p<0.001). The ICI reduction was reversed by intravenous injection of PPADS (†: p<0.001). ICI: intercontraction interval, PS: protamine sulfate, ATP: adenosine 5'-triphosphate, PPADS: pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, PPADS 0.1: PPADS 0.1mg/kg, PPADS 1: PPADS 1mg/kg, PPADS 10: PPADS 10mg/kg.
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Fig. 5
Typical micturition phase. A: Baseline, B: after PS instillation, C: after ATP instillation with PS pretreatment, D: after intravenous injection of PPADS (10mg/kg) during ATP instillation with PS pretreatment. Arrow shows the intraluminal pressure high-frequency oscillations (IPHFOs). PS: protamine sulfate, ATP: adenosine 5'-triphosphate, PPADS: pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid.
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Table 1
Variation of cystometric parameters according to agents
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Data presented as mean±SD. PS: protamine sulfate, ATP: adenosine 5'-triphosphate, PPADS: pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, ICI: intercontraction interval, MVP: maximal voiding pressure, PT: pressure threshold

Table 2
Variation of parameters in voiding phase according to agents
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Data presented as mean±SD. PS: protamine sulfate, ATP: adenosine 5'-triphosphate, PPADS: pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, MBP: maximal bladder pressure

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