title: Nitric oxide-mediated suppression of detrusor overactivity by arginase inhibitor in rats with chronic spinal cord injury.
abstract: OBJECTIVE
  We investigated the effects of an arginase inhibitor on bladder overactivity and measured bladder arginase I and II mRNA levels in rats with chronic spinal cord injury (SCI).
  
  
  METHODS
  We performed awake cystometrograms 3 to 4 weeks after spinal cord transection in female rats. Cystometric parameters such as mean amplitudes and number of non-voiding contractions (NVCs), voided volume, voiding efficiency, and micturition pressure were evaluated before and after intravenous (i.v.) injection of an arginase inhibitor (nor-NOHA: N(omega)-hydroxy-nor-L-arginine) in SCI rats. We also examined the effects of an NOS inhibitor (L-NAME: N(omega)-nitro-L-arginine methyl ester hydrochloride) to determine whether suppression of bladder overactivity by arginase inhibition is mediated by increased production of NO. In addition, we measured mRNA levels of arginase I and II in SCI bladders using quantitative real-time polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  We found that nor-NOHA (10 mg/kg, i.v.) significantly decreased the amplitude and number of NVCs. There were no significant changes in other parameters before and after administration of vehicle or nor-NOHA at any dose. When we administered L-NAME (20 mg/kg, i.v.) before nor-NOHA injection (10 mg/kg, i.v.), nor-NOHA-induced inhibition of NVCs was prevented. The relative levels of both arginase I and II mRNA in the bladder were significantly higher in SCI rats compared with spinal cord-intact rats.
  
  
  CONCLUSIONS
  These results suggest that arginase inhibition can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, arginase inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI.
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors: Kurumi
authors: K
authors: Sasatomi
authors: Shiro
authors: S
authors: Hiragata
authors: Minoru
authors: M
authors: Miyazato
authors: Michael B
authors: MB
authors: Chancellor
authors: Sidney M
authors: SM
authors: Morris
authors: Naoki
authors: N
authors: Yoshimura
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002908:Chronic Disease; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000150:complications / Q000628:therapy*; D013131:Spine / Q000473:pathology; D001743:Urinary Bladder / Q000187:drug effects; D001750:Urinary Bladder, Neurogenic / Q000150:complications / Q000188:drug therapy*
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D001119:Arginase