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Sources of Funding: This work was supported by a Grant-in-Aid for Scientific Research (15K01376 and 15K01377)

Introduction

Age-related symptoms such as urinary retention, poor urine flow, and/or incontinence have been attributed to detrusor underactivity (DU). Our recent data showed that in continuous cystometry, bladder contractility did not diminish but post-void residual urine volume was higher in aging rats than in young rats. Thus, the assumption that bladder and urethral dysfunction occur simultaneously in aging rats seems reasonable. Therefore, we investigated this possibility by measuring time-dependent changes of bladder and urethral functions in rats.

Methods

Female Sprague-Dawley rats (young rats aged 3 months and rats aged 12 and 24 months) were used. 1) Continuous cystometry was performed under awake condition in each group. 2) Urethral activity was evaluated by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia in 3-month-old and 12-month-old rats. 3) Masson's trichrome staining in the bladder was performed in each group.

Results

1) Cystometric evaluations revealed that the intercontraction intervals in the 24-month-old rats were prolonged (p < 0.01) when compared with those in the 3-month-old or 12-month-old rats. In the 24-month-old rats, residual urine volume was significantly higher than in the 3-month-old or 12-month-old rats, and non-voiding contractions were prominent. However, the amplitude of bladder contraction did not differ among the three groups. 2) UPP relaxation (baseline UPP minus nadir UPP) was more significantly diminished (64%) in the 12-month-old rats than in the 3-month-old rats (p < 0.05). The mean rate and amplitude of high-frequency oscillation (HFO) of urethral striated muscle were also significantly lower (12% and 41%, respectively) in the 12-month-old rats than in the 3-month-old rats. 3) In the bladders of the 24-month-old rats, increases in smooth muscle cell hypertrophy and fibrous tissue were observed.

Conclusions

1) Our aging model that focused on bladder function showed increased intercontraction intervals and non-voiding bladder contractions with increased residual urine volume, suggesting detrusor hyperactivity with impaired contractility bladder activity. 2) Our aging model that focused on urethral function indicates urethral dysfunction, as evident from the reduction in HFO activity of the urethral striated muscle and the urethral relaxation. Thus, age-associated bladder and urethral dysfunction seem likely to occur simultaneously, which leads to DU with a vicious cycle.

Funding

This work was supported by a Grant-in-Aid for Scientific Research (15K01376 and 15K01377)