title: Effects of an alpha1A/D-adrenoceptor antagonist, naftopidil, and a phosphodiesterase type 5 inhibitor, tadalafil, on urinary bladder remodeling in rats with spinal cord injury.
abstract: OBJECTIVE
  In order to clarify whether an alpha1A/D-adrenoceptor (α1A/D-AR) antagonist, naftopidil, or a phosphodiesterase type 5 (PDE5) inhibitor, tadalafil, prevents bladder wall remodeling after spinal cord injury (SCI), we examined the bladder and urethral activity as well as ischemic and fibrotic changes in the bladder using SCI rats with or without naftopidil or tadalafil treatment.
  
  
  METHODS
  Adult female Sprague-Dawley rats were divided into four groups: (1) normal (spinal cord intact); (2) vehicle SCI; (3) naftopidil SCI; and (4) tadalafil SCI groups. In SCI groups, rats underwent Th9-10 spinal cord transection followed by oral application of vehicle, naftopidil (20 mg/kg/day) or tadalafil (2 mg/kg/day) for 1, 2, 4, 8, and 12 weeks. Bladder and urethral pressures, mRNA levels of fibrosis-related molecules and ischemia markers and the composition of bladder collagen and elastin were evaluated.
  
  
  RESULTS
  Naftopidil treatment reduced the upregulation of mRNA levels of ischemia and fibrosis markers at the early phase of SCI, and ameliorated the decrease of bladder compliance and voiding efficiency, and the increase of urethral pressure and collagen concentration in the bladder wall at the late phase of SCI. Tadalafil treatment reduced the upregulation of mRNA levels of fibrosis markers, the decrease of bladder compliance and the increase of collagen concentration at the late phase of SCI.
  
  
  CONCLUSIONS
  These results suggest that naftopidil and tadalafil treatments improved the bladder remodeling shown by increased bladder collagen contents after SCI in a different time course. Thus, these treatments could be effective for reducing the SCI-related tissue remodeling in the bladder. Neurourol. Urodynam. 9999:XX-XX, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|Southern Knights' Laboratory, LLP, Okinawa, Japan.|Okinawa Kyodo Hospital, Okinawa, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kadekawa
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Majima
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawamorita
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoshizawa
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Southern Knights' Laboratory, LLP, Okinawa, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Sugaya
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D009281:Naphthalenes / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D000068581:Tadalafil / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D000068581:Tadalafil; C064357:naftopidil
keywords: alpha1A/D-adrenoceptor; bladder; naftopidil; phosphodiesterase type 5 inhibitor; rat; spinal cord injury; tadalafil; urethra