α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury.

Ideal therapy for lower urinary tract dysfunction in patients with spinal cord injury (SCI) should decrease detrusor overactivity, thereby promoting urine storage at low intravesical pressure and promoting efficient voiding at low pressure by decreasing detrusor-sphincter dyssynergia. Here we investigated blockade of various α-adrenoceptors to determine the subtype that was principally responsible for improving the voiding dysfunction. The effects of the intravenous α-blocker naftopidil, the α-blocker BMY 7378, and the α-blocker silodosin were evaluated using cystometrography and external urethral sphincter-electromyography (EMG) in decerebrated, unanesthetized female Sprague-Dawley rats with chronic SCI following transection at Th8. Parameters measured included the voided volume, residual volume, voiding efficiency, and burst and silent periods on EMG. Compared with values in decerebrated non-SCI rats, EMG of decerebrated SCI rats revealed more prominent tonic activity, significantly shorter periods of bursting activity, and a reduced ratio of the silent to active period during bursting. Compared with the value before drug administration (control), the voiding efficiency was significantly increased by naftopidil (1 and 3 mg/kg) (<0.05 each), and the burst (<0.01 and <0.05, respectively) and silent periods (<0.01 each) on EMG were significantly lengthened. BMY 7378 (1 mg/kg) significantly increased voiding efficiency and lengthened the burst periods (<0.05 each). Silodosin did not affect any parameters. These results suggest that α-blockade reduces the urethral resistance associated with detrusor-sphincter dyssynergia, thus improving voiding efficiency in SCI rats.