α1-adrenoceptors in urethral function

The external urethral sphincteric mechanism generates forces which seal the urethra and can be measured as urethral pressure. Resting pressure can be augmented transiently through a reflex pathway during increases in intra;abdominal pressure. The exact role of the various components of the urethral wall that generate this pressure is so far unknown. Urethral contributions to continence come from the mucosal hermetic seal, the submucosa and its vascular filling and the smooth and striated muscle. In humans alpha(1)-adrenoceptor antagonists can reduce urethral pressure, whereas agonists have little effect. A significant part of urethral resting tone is thought to be mediated through the smooth muscles. In vitro, longitudinal and circular smooth muscle components possess spontaneous tone and are innervated by excitatory and inhibitory nerves. Both types possess adrenoceptors and contract on stimulation of intrinsic sympathetic nerves or application of alpha(1)-adrenoceptor agonists. In human urethra, longitudinal smooth muscle predominates but its functional role is unclear. alpha(1) stimulation may also affect the vasculature of the submucosal the striated muscle of the urethra or transmitter release from neurones in the control pathways. Insufficient knowledge of alpha(1)-adrenoceptor distribution and function within the urethra and the surrounding tissues currently prevents accurate prediction of the therapeutic potential of alpha(1)-adrenoceptor ligands.