Inhibitory effect of the urothelium/lamina propria on female porcine urethral contractility & effect of age

The urethral uroepithelium has been implicated in urethral sensation and maintenance of continence. However, relatively little is known about the function of the urethral urothelium compared with that of the bladder. The aim of the study was to examine the role of the urothelium/lamina propria on contractility of the porcine urethra, along with the influence of nitric oxide, prostaglandins and ageing. Porcine urethral tissues, intact and denuded of urothelium/lamina propria, were mounted in tissue baths and contractions to noradrenaline, phenylephrine and carbachol obtained. Contractions in the presence of Nώ–nitro-l-arginine (100 μmol/L) and indomethacin (10 μmol/L) were examined, along with contractions of tissues from young (6 months) and older (3 years) animals. The urothelium/lamina propria of the urethra significantly inhibited contractions to carbachol, noradrenaline and phenylephrine. This inhibitory effect was not significantly different for the three agonists (58.7±10.3%, 60.4±12.6% and 39.4±12.2% inhibition; n=4-7), and was also observed when denuded tissues were co-incubated with a second tissue with intact urothelium/lamina propria (40.6±7.5% inhibition; n=6). Inhibition of nitric oxide and prostaglandin production did not attenuate the inhibitory effect of the urothelium/lamina propria on noradrenaline contractions. In addition, ageing did not alter the inhibitory effect for either phenylephrine contractions (33.9±2.2% vs 41.0±9.7%, young vs older urethral tissues) or noradrenaline contractions (32.9±11.1% vs 53.7±11.0%). In conclusion the urothelium/lamina propria of the urethra has an inhibitory effect on receptor-mediated urethral contraction. This inhibition is due to the release of a diffusible factor, and the effect is not mediated by nitric oxide or prostaglandins, or affected by age.