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

Abstract

AIMS:

To confirm the role of alpha1-adrenoceptor (α(1)-AR) in the spinal cord, we investigated the effect of intrathecal application of terazosin, a non-selective α(1)-AR blocker, on the micturition reflex, as well as the change of α(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 α(1)-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 α(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 μg) 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) α(1)-AR subtype mRNA levels was all increased after SCI.

SIGNIFICANCE:

These results suggest that α(1)-AR facilitates the micturition reflex in the spinal cord, and α(1)-AR blockers applied in the lumbosacral spinal inhibits this effect. Upregulation of α(1)-AR in the lumbosacral spinal cord could be involved in the genesis of detrusor overactivity after SCI. Therefore, if α(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).

• Authors: Minoru Miyazato, Takuma Oshiro, Michael B Chancellor, William C de Groat, Naoki Yoshimura, Seiichi Saito
• Journal: Life sciences (Life Sci) Vol. 92 Issue 2 Pg. 125-30 (Feb 07 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23178151 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Phenylephrine
• Terazosin
• Prazosin

Topics

• Adrenergic alpha-1 Receptor Antagonists (therapeutic use)
• Animals
• Female
• Phenylephrine (pharmacology)
• Prazosin (analogs & derivatives, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (drug effects, physiopathology)
• Spinal Cord Injuries (drug therapy, physiopathology)
• Urinary Bladder (drug effects, physiopathology)
• Urination (drug effects, physiology)