A new method for producing urinary bladder hyperactivity using a non-invasive transient intravesical infusion of acetic acid in conscious rats

Mitobe, Manabu; Inoue, Hirokazu; Westfall, Timothy D.; Higashiyama, Hiroyuki; Mizuyachi, Kaori; Kushida, Hiroshi; Kinoshita, Mine

doi:10.1016/j.vascn.2007.12.001

Cited by 22 publications

(17 citation statements)

References 16 publications

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“…These results are similar to those from a study in the rat which found similar damage of urothelium and lamina propria and infiltration of neutrophils and/or macrophages 9 hours following only 5 minutes of 0.75% acetic acid infusion in the bladder [48]. …”

Section: Discussionsupporting

confidence: 90%

Stability of the Acetic Acid-Induced Bladder Irritation Model in Alpha Chloralose-Anesthetized Female Cats

Kullmann¹,

Wells²,

Langdale³

et al. 2013

PLoS ONE

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Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min “quiet period” (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8th. Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function.

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Section: Discussionsupporting

confidence: 90%

Stability of the Acetic Acid-Induced Bladder Irritation Model in Alpha Chloralose-Anesthetized Female Cats

Kullmann¹,

Wells²,

Langdale³

et al. 2013

PLoS ONE

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“…Acetic acid solutions have been shown to evoke a statistically significant increase in voiding frequency and intravesical pressure in conscious rats (McCafferty et al, 2008; Mitobe et al, 2008). Here we showed that acetic acid-induced changes are coupled with a higher frequency of sensory neural activity.…”

Section: Discussionmentioning

confidence: 99%

A Non-Anesthetized Mouse Model for Recording Sensory Urinary Bladder Activity

Zvara¹,

Wright²,

Roach³

et al. 2010

Front. Neur.

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The goal of this study was to develop an in vivo awake mouse model for extracellular bladder sensory nerve recording. A bipolar 125-μm silver electrode was positioned under a single postganglionic bladder nerve. Efferent nerve signals were eliminated by tying off the postganglionic bladder nerve between the major pelvic ganglion and the recording electrode. Sensory nerve activity was measured in the conscious animals 48 h after surgery during continuous intravesical infusion of 0.9% saline/0.5% acetic acid followed by 0.5% acetic acid with capsazepine (10 μM) at a rate of 0.75 ml/h. Continuous infusion of 0.9% NaCl led to a gradual increase in the frequency of sensory nerve firing that peaked upon reaching threshold pressure. Non-micturition contractions were observed in some animals during filling and other animals exhibited only minimal pressure fluctuations; both types of events were associated with a rise in sensory nerve activity. Intravesical infusion of 0.5% acetic acid reduced the intermicturition interval. This was associated with a 2.1-fold increase in bladder pressure during filling and a two-fold increase at both threshold and micturition pressures. Concurrent with these changes, sensory activity increased 2.8-fold during filling and 2.4-fold at threshold pressure. Subsequent intravesical infusion of capsazepine in 0.5% acetic acid reduced filling and threshold pressures by 21 and 31.2%, respectively, and produced corresponding decreases of 36 and 23.4% in sensory nerve activity. The current study shows that multifiber sensory nerve recordings can be reproducibly obtained from conscious mice.

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“…The role of the bladder urothelium in OAB has only been investigated in the context of the vanilloid receptor TRPV1 and muscarinic receptor expression (9, 10). Various animal models purported to mimic OAB syndrome have been developed and are used to determine the contribution of urothelium to OAB (5,8,13). While no perfect animal model for OAB exists, investigators have used acetic acid infusion into bladder, bladder outlet obstruction, and cyclophosphamide-induced inflammation to explore how different physiologic mechanisms regulate bladder function.…”

Section: Discussionmentioning

confidence: 99%

Augmented bladder urothelial polyamine signaling and block of BK channel in the pathophysiology of overactive bladder syndrome

Li¹,

Sun²,

Simard

et al. 2009

American Journal of Physiology-Cell Physiology

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Overactive bladder syndrome (OAB) is an idiopathic condition characterized by urinary urgency and urge incontinence. Detrusor overactivity has been traditionally described as the physiologic mechanism for OAB. However, the bladder urothelium (BU) may also be involved in the pathophysiology. This study measured polyamine signaling and its downstream effects on membrane conductivity in bladder urothelial cells (BUC) obtained from asymptomatic and OAB subjects. Immunohistofluorescence was used to measure ornithine decarboxylase (ODC) expression in BU. BUC, cultured from BU biopsies, were used for electrophysiologic studies. dl-alpha-Difluoromethylornithine (DFMO), spermine, or spermidine was used to modulate polyamine signaling in BUC. Results showed ODC overexpression in OAB BU. In OAB BUC, whole cell and cell-attached configuration showed significantly decreased currents. Using inside-out patches, outward currents increased significantly, suggesting a cytoplasmic source of the outward current block in OAB BUC. In control BUC, outward currents were mediated by the large-conductance calcium-activated potassium (BK) channel due to calcium dose-dependence and block by iberiotoxin. Spermidine and spermine blocked the outward current in normal BUC in dose-dependent fashion. Conversely, DFMO significantly increased (P < 0.01) outward currents in OAB BUC both in cell-attached and in whole cell configuration. The outward currents in DFMO-treated-OAB BUC could be significantly reduced (P < 0.05) by adding back spermidine and spermine. These data suggest that polyamine signaling is upregulated in OAB urothelium and OAB BUC. Furthermore, polyamines in BUC block the BK channel. Targeting of bladder urothelial polyamine signaling may represent a novel approach for OAB treatment based on pathophysiologic mechanisms.

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A new method for producing urinary bladder hyperactivity using a non-invasive transient intravesical infusion of acetic acid in conscious rats

Cited by 22 publications

References 16 publications

Stability of the Acetic Acid-Induced Bladder Irritation Model in Alpha Chloralose-Anesthetized Female Cats

Stability of the Acetic Acid-Induced Bladder Irritation Model in Alpha Chloralose-Anesthetized Female Cats

A Non-Anesthetized Mouse Model for Recording Sensory Urinary Bladder Activity

Augmented bladder urothelial polyamine signaling and block of BK channel in the pathophysiology of overactive bladder syndrome

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