title: An alpha1-adrenoceptor blocker terazosin improves urine storage function in the spinal cord in spinal cord injured rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan. miyaz929@med.u-ryukyu.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.forename: Takuma
authors.initials: T
authors.lastname: Oshiro
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Seiichi
authors.initials: S
authors.lastname: Saito
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014554:Urination / Q000187:drug effects* / Q000502:physiology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010656:Phenylephrine; C041226:Terazosin; D011224:Prazosin