Sex-related differences in activity of lower urinary tract in response to intravesical acid irritation in decerebrate unanesthetized mice

Takezawa K, Kondo M, Kiuchi H, Soda T, Takao T, Miyagawa Y, Tsujimura A, Nonomura N, Shimada S. Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis. Am J Physiol Renal Physiol 307: F234 -F241, 2014. First published May 7, 2014 doi:10.1152/ajprenal.00043.2014.-Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction. bladder ultrasonography; cystometry; mouse; LPS; cystitis VARIOUS DISEASES CAUSE BLADDER dysfunction with lower urinary tract symptoms (11). Some diseases, such as overactive bladder, interstitial cystitis, and neurogenic bladder, lead to storage failure, and other diseases, such as underactive bladder and bladder neck construction, lead to voiding failure. Objective evaluation of bladder function is indispensable for accurate diagnosis and development of appropriate treatment strategy for these diseases. Bladder ultrasonography, which can evaluate postvoiding residual volume and bladder wall thickness, is noninvasive and the most common examination for bladder function (5). Cystometry, which can identify detrusor overactivity, low bladder compliance (BCP), and sensory urgency, is an invasive but gold standard examination for bladder function (8). Thus these ex...

Section: Validity Of the New Cystometry Methods With The Catheter Placsupporting

confidence: 67%

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confidence: 99%

Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis

Takezawa

Kondo

Kiuchi

et al. 2014

“…Voiding efficiency (VE; % of bladder volume voided) was estimated as (VV/VT) ϫ 100. Other evaluated parameters were pressure threshold (PT; mmHg) for inducing a voiding contraction, maximal voiding pressure (MVP; mmHg), closing peak pressure (CPP; mmHg), postvoid resting pressure (RP; mmHg), bladder contraction duration (BCD; s), and bladder compliance (BCP; l/mmHg) (18,20). BCP was calculated as the ratio of the infused volume to the pressure difference between two time points at the RP and the PT.…”

Section: Experimental Protocolmentioning

confidence: 99%

Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats

Yoshiyama

Roppolo

Takeda

et al. 2013

Self Cite

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01-0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6-1.2 g/kg (iv) markedly decreased CPP by 69-85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001-0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.

“…A recent study (54) revealed sex-specific differences in activity of the lower urinary tract (LUT) responding to intravesical acetic acid (AA) infusion in decerebrate unanesthetized mice. The study demonstrated that female bladders are more sensitive to the noxious stimulation than male bladders, implying an association between sex and bladder sensitivity to irritation.…”

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confidence: 99%

“…Therefore, this study was conducted in both females and males by intravesically infusing capsazepine, a selective TRPV1 antagonist, to examine the possible involvement of TRPV1 in activity of the LUT in response to AA irritation. Decerebrate unanesthetized mice (54) were used to avoid possible artifacts caused by behavioral responses and movements of awake animals that receive persistent intravesical irritant during cystometry (6,34) and anesthesiainduced suppressions of the LUT activity (27,56,61). Moreover, to facilitate better understanding of the complex autonomic functions, we used detailed cystometric evaluations (54).…”

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confidence: 99%

Functional roles of TRPV1 channels in lower urinary tract irritated by acetic acid: in vivo evaluations of the sex difference in decerebrate unanesthetized mice

Yoshiyama

Araki

Kobayashi

et al. 2010

Self Cite

Sex-specific differences in activity of the lower urinary tract (LUT) responding to acid irritation in mice have been revealed. This study, using continuous infusion cystometry with acetic acid (AA; pH 3.0), was conducted to examine whether the transient receptor potential vanilloid type 1 (TRPV1) channels expressed in the mouse LUT are involved in the sex difference in functional responses of the bladder and urethra to irritation. No differences were found between effects of capsazepine (a TRPV1 blocker; 100 microM) and those of its vehicle on any of the cystometric changes by intravesical AA in either female or male mice. However, capsazepine eliminated the acid-induced sex differences in parameters associated with bladder contraction phase (i.e., maximal voiding pressure, closing peak pressure, 2nd-phase contraction, bladder contraction duration), whereas capsazepine did not affect those in parameters associated with bladder-filling period (i.e., intercontraction interval, actual collecting time). In males, capsazepine reduced the number of bladder contractions accompanying fluid dribbling at 2nd-phase contraction, which is indicative of the urethral response to irritation, whereas in females it increased the number. Together, these results suggest the possibilities that TRPV1 channels in the bladder and urethra are involved in the sex difference in the LUT response to acid irritation and that these participate, e.g., via "cross talk" between the bladder and urethra, in the fine-tuning of intravesical pressure (or bladder emptying) at the bladder contraction phase under irritated LUT conditions but not in sensing for bladder filling during the storage period, although the contribution of the mechanism may be small.