Detrusor Overactivity After Partial Bladder Outlet Obstruction Is Associated With High Urinary Adenosine Triphosphate Levels in Female Wistar Rats
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Purpose: Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels. Methods: Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chisquare and Mann-Whitney tests. Results: DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO. Conclusions: The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.
Abstract
Purpose: Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels. Methods: Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chisquare and Mann-Whitney tests. Results: DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO. Conclusions: The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.
참고문헌 (28)
- Oelke M, "Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia", Eur Urol, 54, pp.419~426 (2008)
- Chen SF, "Change of detrusor contractility in patients with and without bladder outlet obstruction at ten or more years of follow-up", Sci Rep, 9, pp.18887~ (2019)
- Irwin DE, "Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries : results of the EPIC study", Eur Urol, 50, pp.1306~1315 (2006)
- Levin RM, "Studies on experimental bladder outlet obstruction in the cat : long-term functional effects", J Urol, 148, pp.939~943 (1992)
- Saito M, "Effect of partial outlet obstruction on contractility : comparison between severe and mild obstruction", Neurourol Urodyn, 12, pp.573~583 (1993)
- Drake MJ, "The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity", BJU Int, 119, pp.22~29 (2017)
- Steers WD, "Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction", J Comp Neurol, 310, pp.401~410 (1991)
- Shiina K, "ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet obstruction", Biomed Res, 37, pp.299~304 (2016)
- Vlaskovska M, "P2X3 knock-out mice reveal a major sensory role for urothelially released ATP", J Neurosci, 21, pp.5670~5677 (2001)
- Birder LA, "How does the urothelium affect bladder function in health and disease? ICI-RS 2011", Neurourol Urodyn, 31, pp.293~299 (2012)
- Cockayne DA, "Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice", Nature, 407, pp.1011~1015 (2000)
- Friedrich C, "Safety, pharmacodynamics, and pharmacokinetics of P2X3 receptor antagonist eliapixant(BAY 1817080)in healthy subjects : doubleblind randomized study", Clin Pharmacokinet, 61, pp.1143~1156 (2022)
- Vale L, "DU is induced by low levels of urinary ATP in a rat model of partial bladder outlet obstruction : the incidence of both events decreases after deobstruction", Adv Urol, 2022, pp.6292457~ (2022)
- Van Koeveringe GA, "Detrusor underactivity : pathophysiological considerations, models and proposals for future research. ICI-RS 2013", Neurourol Urodyn, 33, pp.591~596 (2014)
- Nomiya M, "Progressive vascular damage may lead to bladder underactivity in rats", J Urol, 191, pp.1462~1469 (2014)
- Ferguson AC, "Inhibition of urothelial P2X3 receptors prevents desensitization of purinergic detrusor contractions in the rat bladder", BJU Int, 116, pp.293~301 (2015)
- Beckel JM, "Pannexin 1 channels mediate the release of ATP into the lumen of the rat urinary bladder", J Physiol, 593, pp.1857~1871 (2015)
- Silva-Ramos M, "Increased urinary adenosine triphosphate in patients with bladder outlet obstruction due to benign prostate hyperplasia", Prostate, 76, pp.1353~1363 (2016)
- Chen Z, "Urinary ATP may be a biomarker for bladder outlet obstruction and its severity in patients with benign prostatic hyperplasia", Transl Androl Urol, 9, pp.284~294 (2020)
- Steers WD, "Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function", J Clin Invest, 88, pp.1709~1715 (1991)
- Elbadawi A, "Structural basis of geriatric voiding dysfunction. III. Detrusor overactivity", J Urol, 150(5Pt 2), pp.1668~1680 (1993)
- Markham A, "Gefapixant : first approval", Drugs, 82, pp.691~695 (2022)
- Tempest HV, "P2X2 and P2X3 receptor expression in human bladder urothelium and changes in interstitial cystitis", BJU Int, 93, pp.1344~1348 (2004)
- Jiang YH, "Urothelial dysfunction, suburothelial inflammation and altered sensory protein expression in men with bladder outlet obstruction and various bladder dysfunctions : correlation with urodynamics", J Urol, 196, pp.831~837 (2016)
- Ito K, "Therapeutic effects of the putative P2X3", P2X2, Naunyn Schmiedebergs Arch Pharmacol, pp.2008, 377[DOI]
- Gao XF, "Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3", Nat Commun, 6, pp.7650~ (2015)
- Ewerton F, "Efficacy and safety of eliapixant in overactive bladder : the 12-week, randomised, placebo-controlled phase 2a OVADER study", Eur Urol Focus (2023)[DOI]
- Dicpinigaitis PV, "Efficacy and safety of eliapixant in refractory chronic cough : the randomized, placebo-controlled phase 2b PAGANINI study", Lung, 201, pp.255~266 (2023)