MP68-12 IN VITRO RELAXING RESPONSE OF PHOSPHODIESTERASE-5 INHIBITORS AND β-ADRENOCEPTOR AGONISTS IN MICE BLADDER

Abstract

during voiding; however, NO decreases with age. Thus, it seems reasonable to assume that urethral relaxation during voiding also decreases in aging rats. We therefore investigated this possibility by measuring urethral relaxation before and after intravenous injection of NO synthase and an inhibitor in aging rats.METHODS: Female Sprague Dawley rats (young rats aged 3 months and old rats aged 12~15 months) were used. 1) Urethral activity was evaluated by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) under urethane anesthesia. 2) Under isovolumetric conditions, L-arginine (a substrate of NO synthase, 100 mg/kg) was administered intravenously in both groups. 3) In addition, L-NAME (an NO synthase inhibitor, 100 mg/kg) was also administered intravenously in both groups.RESULTS: 1) UPP nadir during urethral relaxation was significantly higher (34%) in aging rats than that in young rats (p<0.05), whereas baseline UPPs were not significantly different. The mean rate and amplitude of high frequency oscillation (HFO) of urethral striated muscle were also significantly lower (12% and 41%, respectively) in aging rats than those in normal rats (p<0.05). 2) Following L-arginine (i.v.), UPP nadir did not change in both groups. 3) However, UPP nadir during urethral relaxation was inhibited by L-NAME (i.v.) in both groups. The effect was greater in aging rats (i.e., a detrusor sphincter dyssynergia like change) than in young rats.CONCLUSIONS: These results indicate that aging induces dysfunction in urethral relaxation during voiding, as evidenced by a decrease in HFO activity of urethral striated muscle as well as NO mediated urethral relaxation of urethral smooth muscle. Thus, it seems likely that these urethral dysfunctions caused by accruing age may lead to inefficient voiding with increased post-void residual urine volume (DU), which is often observed in elderly populations. This novel study coupled with DU would contribute to elucidate the mechanisms in the genesis of aging bladders.