An alpha1-adrenoceptor blocker terazosin improves urine storage function in the spinal cord in spinal cord injured rats

Aims: To confirm the role of alphal-adrenoceptor (alpha(1)-AR) in the spinal cord, we investigated the effect of intrathecal application of terazosin, a non-selective alpha(1)-AR blocker, on the micturition reflex, as well as the change of alpha(1)-AR subtypes mRNA in the lumbosacral spinal cord using spinal cord injury (SCI) rats. Main methods: Adult female Sprague-Dawley rats were used 4 weeks after Th9-10 spinal cord transection. 1) Continuous cystometry was performed under an awake condition to examine the effect of intrathecal terazosin, a non-selective alpha(1)-AR blocker, at the level of L6-S1 spinal cord. 2) We also investigated the effect of intravenous phenylephrine, an alpha 1-AR agonist, with or without intrathecal terazosin. 3) Quantification of alpha(1)-AR subtype mRNA in the L6-S1 lumbosacral spinal cord was performed in normal and SCI rats. Key findings: 1) Terazosin (0.01-10 mu g) inhibited the number of non-voiding bladder contractions, and increased bladder capacity by 73%. 2) Phenylephrine (0.1 mg/kg) reduced bladder capacity by 17%, and voiding efficiency by 20%. Intrathecal terazosin blocked the effect of intravenous phenylephrine. 3) alpha(1)-AR subtype mRNA levels was all increased after SCI. Significance: These results suggest that alpha(1)-AR facilitates the micturition reflex in the spinal cord, and alpha(1)-AR blockers applied in the lumbosacral spinal inhibits this effect. Upregulation of alpha(1)-AR in the lumbosacral spinal cord could be involved in the genesis of detrusor overactivity after SCI. Therefore, if alpha(1)-AR blockers pass the blood-brain barrier, they could act in the spinal cord to improve storage function in patients with detrusor overactivity (DO). (C)2012 Elsevier Inc. All rights reserved.