Abstract
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.
Highlights
Bladder and urethra store and periodically release urine in a coordinated manner
Many acute overactive bladder (OAB) [8,11,25,26] and stress urinary incontinence (SUI) [10,27] models frequently employ bladder irritation, commonly using dilute acetic acid (0.25-0.5%). This acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats has been used for many years in various pharmacological and physiological studies of lower urinary tract (LUT) function, the stability across time and multiple vehicle administrations has not been published
In this study we evaluate the stability of bladder and rhabdosphincter EMG activity during a 6-7 hour experiment with 7 intravenous saline vehicle injections to mimic a dose–response protocol
Summary
Bladder and urethra store and periodically release urine in a coordinated manner. Voiding is achieved via release of acetylcholine/adenosine triphosphate (ACh/ATP) and nitric oxide (NO) from the parasympathetic fibers to concomitantly contract the bladder and relax the urethra, respectively [1]. Continence during the storage phase is achieved via tonic release of norepinephrine (NE) to relax the bladder and contract the urethra. Many acute OAB [8,11,25,26] and SUI [10,27] models frequently employ bladder irritation, commonly using dilute acetic acid (0.25-0.5%) This acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats has been used for many years in various pharmacological and physiological studies of LUT function, the stability across time and multiple vehicle administrations (i.e. across a 5-8 hour period required for multiple drug administrations to create cumulative dose–response characteristics and antagonist administration) has not been published. We include an intravenous administration of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, at the end of the current standardized protocol to compare its effects with previous studies [10]
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