785 EFFECT OF AGING ON URETHRAL AND BLADDER FUNCTION OF RATS

INTRODUCTION AND OBJECTIVES: The prevalence of stress urinary incontinence increases with age, suggesting that age-related changes may influence its development. It remains poorly understood how factors such as aging, parturition, and hormones contribute to these changes. The purpose of this study is to evaluate the effects of aging on the urethra and bladder of female Sprague-Dawley (SD) rats. METHODS: Nulliparous female SD rats (n 52) were divided into two groups: young rats (3–15 months, mean: 8 months) and older rats (16 –24 months, mean: 18 months). All animals underwent cystometry and evaluation of abdominal leak point pressure (ALPP). Urethral resistance was evaluated by retrograde urethral perfusion pressure (RUPP). After sacrificing the animals, muscarinic receptor activation was tested on urethral and bladder strips in isometric studies. Harvested tissue from both groups was evaluated for apoptosis with TUNEL staining, neural innervation with the neuronalspecific marker PGP 9.5, urothelial thickness, amount of blood vessels, and extracellular matrix to smooth muscle ratio with Masson’s trichrome staining. RESULTS: Cystometry revealed a similar baseline bladder capacity in young and older rats when adjusted to their body weight. Urodynamic studies showed a significant lower ALPP (p 0.000) and RUPP (p 0.0003) in older animals when compared to young. Older rats’ bladder strips were statistically less contractile than those of young rats when responses were tested to KCl (p 0.03), carbachol (p 0.03), and isoproterenol (p 0.00). A similar trend was seen in urethral contractility. Histological evaluation demonstrated thinning of the urothelial layer in urethral tissue (p 0.022) of the aging rat. The smooth muscle content was decreased in the bladder and urethral tissue of aged animals. There was an increase in apoptotic cells in the older rat urethral (p 0.021) and bladder (p 0.035) tissue in comparison to tissue from young animals. CONCLUSIONS: Older rats have lower baseline urethral resistance and decreased contractility in comparison to younger animals. Histological changes, such as thinning of the urothelium, decrease of smooth muscle content and an increase of apoptotic cells, were observed in older rats and point to a possible mechanism for the observed changes in voiding dynamics. These findings mimic those seen in humans and therefore naturally aging SD rats appear to provide an excellent animal model to study the pathophysiology of SUI with respect to age.