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

Life Sci. 2013 Feb 7;92(2):125-30. doi: 10.1016/j.lfs.2012.11.006. Epub 2012 Nov 21.

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

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