alpha1-adrenoceptors in urethral function

Abstract

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 alpha1-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 alpha1-adrenoceptors and contract on stimulation of intrinsic sympathetic nerves or application of alpha1-adrenoceptor agonists. In human urethra, longitudinal smooth muscle predominates but its functional role is unclear. alpha1 stimulation may also affect the vasculature of the submucosa, the striated muscle of the urethra or transmitter release from neurones in the control pathways. Insufficient knowledge of alpha1-adrenoceptor distribution and function within the urethra and the surrounding tissues currently prevents accurate prediction of the therapeutic potential of alpha1-adrenoceptor ligands.