Aging causes changes in bladder activity including detrusor hyperactivity with impaired contractile function. Data from a previous study showed that bladder contractility in aged rats decreased when under urethane anesthesia but was not diminished in normal conditions. Post-void residual urine volume was increased in both conditions in older rats than in young rats. However, there have been few studies on changes in urethral activity by age. We investigated this discrepancy by studying urethral function in rats of varying ages by simultaneously recording intravesical pressure, urethral perfusion pressure (UPP), and external urethral sphincter electromyography (EUS-EMG).

Female Sprague-Dawley rats aged 3 months (young rats), 12 months (middle-aged rats), and 24 months (aged rats) were used study. Urethral activity was evaluated by simultaneously recording intravesical pressure and UPP under isovolumetric conditions under urethane anesthesia in each group. EUS-EMG activity was also monitored under the same conditions. L-arginine (a substrate of nitric oxide synthase, 100 mg/kg) or NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 100 mg/kg) was then administered to each group to confirm the role of urethral smooth muscle activity. Bungarotoxin (neuromuscular blocker, 375 µg/kg) was also administered to confirm the role of EUS activity. Masson’s trichrome staining in the urethra was performed in each group.

The amplitude of bladder contractions in aged rats was decreased in comparison to the middle-aged and young rats. UPP change, defined as UPP nadir minus baseline UPP, was significantly smaller in aged rats (60%) and middle-aged rats (64%) than in young rats (P<0.05). The mean amplitude of high-frequency oscillations (HFOs) of EUS was also significantly lower in aged rats (62%) and middle-aged rats (70%) than in young rats (P < 0.05). In middle-aged rats, urethral contraction during UPP change (i.e., impaired urethral relaxation) was noted and restored by L-arginine. UPP nadir during bladder contraction was inhibited by L-NAME in each group of rats. In 3 out of 4 aged rats and 3 out of 9 middle-aged rats showed a detrusor-sphincter dyssynergia pattern after L-NAME was administered. However, UPP nadir was not changed by L-NAME in young rats. Bungarotoxin completely inhibited HFOs and EUS-EMG bursting activity in all rats. Masson’s trichrome staining of the urethra showed EUS hypotrophy in aged rats compared to young and middle-aged rats.

UPP change was significantly lesser in aged rats (60%) and middle-aged rats (64%) than in young rats. In EUS-EMG, EUS-bursting activity was seen during voiding phase that reflects rhythmic opening and closing of the outlet to produce pulsatile flow of urine to help with efficient bladder emptying. The active phase and silent phase in EUS-bursting activity were clearly seen in young rats but not in aged rats. These results suggest that NO-mediated relaxation of urethral smooth muscle (i.e., UPP change) and EUS-mediated pumping activity diminish with age. Bladder contractility was most diminished (63%) in aged rats, but in middle-aged rats, UPP change was 64% and the HFO of EUS was 70% compared with young rats. This suggests that urethral dysfunction on aging is likely to occur at an earlier phase than bladder dysfunction, which can likely lead to detrusor underactivity and an elevation in residual urine volume.

The results indicate that aging induces dysfunction in movement coordination between the urinary bladder and urethra. Urethral dysfunction on aging seems to occur at an earlier phase than bladder dysfunction, which may affect the coordination of actions between the bladder and urethra. Moreover, bladder and urethral physiological change were seen in aged rats. Therefore, age-associated urethral dysfunctions may lead to inefficient voiding with increased post-void residual urine volume, which is often observed in elderly human populations. These results assist in clarifying the mechanism of physiological changes of bladder function in aging populations.