Studies have demonstrated that the urothelium may play an inhibitory role in modulating detrusor smooth muscle contractility. We studied possible mechanisms involved in urothelial regulation of detrusor smooth muscle tone.

 

Methods:

One half of each bladder obtained from 15 male New Zealand white rabbits were de-mucosalized. Longitudinal strips of each bladder body were weighed and processed for isometric tension measurement. In strips with urothelium (Uro+) and without urothelium (Uro-), the reactivity to electrical field stimulation (EFS), carbachol, methoxamine and isoproteronol were studied at baseline tension. The reactivity to EFS and carbachol was then re-examined following tissue treatment with atropine, guanethidine, indomethacin and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor.

 

Results:

Removal of the urothelium altered spontaneous contractility of the bladder strips. At baseline, Uro- strips demonstrated significant increases in the frequency, amplitude and duration of spontaneous contractions and in contractile response to EFS, carbachol and methoxamine relative to Uro+ strips. The contractile response of Uro- strips to EFS and carbachol were not significantly altered in the sole presence of indomethacin. However, they were significantly reduced in the presence of NDGA, and more so with NDGA + indomethacin. In the presence of atropine, both Uro+ and Uro- strips demonstrated a similar decrease in contractile response to EFS and carbachol. Guanethidine failed to normalize the differences in the contractility of Uro- and Uro+ bladder strips. Relaxation responses to the beta adrenergic agonist isoproteronol were significantly reduced in the Uro- strips.

 

Conclusions:

Removal of the urothelium resulted in significant increases in baseline contractile instability and the contractile response of isolated rabbit bladder strips to EFS, carbachol, and methoxamine, while impairing the relaxatory response to isoproteronol. These observations confirm the inhibitory effect of the urothelium on bladder tone. The significant reduction of hypercontractility in Uro- strips in the presence of NDGA suggests a regulatory role for leukotrienes. These agents are known to directly cause smooth muscle contraction. In Uro- tissues, the observed loss of detrusor inhibition normally induced by isoproterenol suggests an important role for the bladder urothelium in adrenergic control over bladder contractility. Urothelial injury may thus be an important mechanism in the development of detrusor instability and other conditions characterized by detrusor overactivity.