Urothelium dependent inhibition of rat ureter contractile activity

We investigated whether urothelium modulates isolated rat ureter contractions.

Segments of intact and urothelium-free ureters were placed in organ baths at 37C. The contractile effects of KCl and endogenous ureteral contractile agents were recorded in the absence and presence of the cyclooxygenase inhibitors indomethacin (1 microM) or ketoprofen (10 microM). The effect of the prostacyclin analogue iloprost was tested on the KCl and agonist induced responses obtained in the presence of ketoprofen.

Without stimulation ureters were quiescent but spontaneous contractions often developed in urothelium-free ureters. Sensitivity to KCl was greater in the absence of urothelium. In intact ureters neurokinin A and vasopressin induced rhythmic contractions, whereas carbachol, norepinephrine, bradykinin and angiotensin II were inactive. In urothelium-free ureters the response to neurokinin A and vasopressin was enhanced and the other agonists, except norepinephrine, promoted contractions. In the presence of cyclooxygenase inhibitors intact ureters responded to carbachol, bradykinin and angiotensin II, and the response to neurokinin A, vasopressin and KCl increased. Responses obtained in urothelium-free ureters were not affected by the presence of cyclooxygenase inhibitors. In the presence of ketoprofen iloprost antagonized the KCl and agonist induced contractile effects in intact but not in urothelium-free ureters.

Data suggest that the urothelium prevents spontaneous contractile activity and decreases the potential excitatory effects of endogenous contractile agents on ureteral motility. The mechanism underlying this inhibitory effect appears to involve the participation of a urothelial cyclooxygenase product such as prostacyclin, which could activate the release of urothelium derived relaxing factor(s) that are as yet unknown.