Age is associated with reduced urethral pressure and afferent activity in rat.

Age-related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age-related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra-to-bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4-7 months) and old (18-24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age-related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age-related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age.

Sensitivity of urethral flow-evoked voiding reflexes decline with age in the rat: insights into age-related underactive bladder.

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help in the development of new treatments by identifying mechanistic targets. In this work, we studied the relationship between age and systems-level function of the LUT and tested the hypothesis that aging is related to weakening of reflexes that control voiding. Three groups of anesthetized female rats, young (4-7 mo old), mature (11-14 mo old), and old (18-24 mo old), were used to quantify the effect of aging on LUT reflexes. A double-lumen catheter enabled us to control the bladder volume and urethral flow rate independently, under quasi-isovolumetric bladder conditions. We systematically investigated the reflex bladder contractions evoked by combinations of rates of urethral infusion and bladder fill volumes as a function of age. Urethral infusion with the same flow rate evoked bladder contractions (via the augmenting reflex) in old animals less often than in younger animals. Furthermore, old animals needed more fluid in their bladders (relative to their bladder capacity) before urethra flow-evoked bladder contractions could be triggered at all, suggesting a delay in the switch of the LUT to "voiding mode." Old rats also showed longer and weaker bladder contractions than young or mature rats. Taken together, this suggests there is an age-related functional weakening and loss of sensitivity in LUT reflexes, which may contribute to age-related UAB symptoms.