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

Abstract

AimsTo confirm the role of alpha1-adrenoceptor (α1-AR) in the spinal cord, we investigated the effect of intrathecal application of terazosin, a non-selective α1-AR blocker, on the micturition reflex, as well as the change of α1-AR subtypes mRNA in the lumbosacral spinal cord using spinal cord injury (SCI) rats. Main methodsAdult female Sprague–Dawley rats were used 4weeks 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 α1-AR blocker, at the level of L6-S1 spinal cord. 2) We also investigated the effect of intravenous phenylephrine, an α1-AR agonist, with or without intrathecal terazosin. 3) Quantification of α1-AR subtype mRNA in the L6-S1 lumbosacral spinal cord was performed in normal and SCI rats. Key findings1) Terazosin (0.01–10μg) inhibited the number of non-voiding bladder contractions, and increased bladder capacity by 73%. 2) Phenylephrine (0.1mg/kg) reduced bladder capacity by 17%, and voiding efficiency by 20%. Intrathecal terazosin blocked the effect of intravenous phenylephrine. 3) α1-AR subtype mRNA levels was all increased after SCI. SignificanceThese results suggest that α1-AR facilitates the micturition reflex in the spinal cord, and α1-AR blockers applied in the lumbosacral spinal inhibits this effect. Upregulation of α1-AR in the lumbosacral spinal cord could be involved in the genesis of detrusor overactivity after SCI. Therefore, if α1-AR blockers pass the blood–brain barrier, they could act in the spinal cord to improve storage function in patients with detrusor overactivity (DO).