과민성 방광모델로서 자연발생 고혈압 쥐에서 비마취하 요역동학 검사로 관찰한 항콜린성 제제인 tolterodine의 배뇨 압력 및 용적에 대한 경구 및 주사 효과
The Effect of tolterodine Via Oral and Intravenous Administrations on Voiding in Awake Spontaneously Hypertensive Rats as an Overactive Bladder Model
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Purpose: We investigated the effect of oral or intravenous tolterodine on cystometric parameters in awake spontaneously hypertensive rats (SHRs) as a model of overactive bladder (OAB). The aim of our study was to observe the experimental conditions required to reproduce the clinical pharmacological effects of tolterodine, as seen in humans, to decrease bladder pressure or increase bladder capacity. Materials and methods: We studied the effects of the most widely used antimuscarinic drug, tolterodine, on cystometric parameters via two different administrations (oral and intravenous) in awake SHRs. Results: Oral administration of tolterodine 10 mg/kg-1 body weight in awake rats did not change any cystometric parameters significantly. Intravenous administration of tolterodine 0.3 mg/kg-1 body weight significantly decreased basal pressure (BP) and micturition pressure (MP), but showed no effect on micturition interval (MI) or bladder capacity (BC). Conclusion: Despite a high dose of tolterodine via an oral or an intravenous route, a decrease in BP or MP was the only effect on cystometrographic parameters in awake rats, whereas MI and BC were not significantly affected. Therefore, it is difficult to reproduce in awake rats as an acute response the cystometric increase in the MI that is observed in humans after chronic administration of antimuscarinic agents.
Abstract
Purpose: We investigated the effect of oral or intravenous tolterodine on cystometric parameters in awake spontaneously hypertensive rats (SHRs) as a model of overactive bladder (OAB). The aim of our study was to observe the experimental conditions required to reproduce the clinical pharmacological effects of tolterodine, as seen in humans, to decrease bladder pressure or increase bladder capacity. Materials and methods: We studied the effects of the most widely used antimuscarinic drug, tolterodine, on cystometric parameters via two different administrations (oral and intravenous) in awake SHRs. Results: Oral administration of tolterodine 10 mg/kg-1 body weight in awake rats did not change any cystometric parameters significantly. Intravenous administration of tolterodine 0.3 mg/kg-1 body weight significantly decreased basal pressure (BP) and micturition pressure (MP), but showed no effect on micturition interval (MI) or bladder capacity (BC). Conclusion: Despite a high dose of tolterodine via an oral or an intravenous route, a decrease in BP or MP was the only effect on cystometrographic parameters in awake rats, whereas MI and BC were not significantly affected. Therefore, it is difficult to reproduce in awake rats as an acute response the cystometric increase in the MI that is observed in humans after chronic administration of antimuscarinic agents.
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