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

Katsumi Kadekawa, Tsuyoshi Majima, Naoki Kawamorita, Hiroki Okada, Tsuyoshi Yoshizawa, Kenichi Mori, Pradeep Tyagi, Kimio Sugaya, Naoki Yoshimura

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aims: 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.

Original languageEnglish
Pages (from-to)1488-1495
Number of pages8
JournalNeurourology and Urodynamics
Volume36
Issue number6
DOIs
Publication statusPublished - 2017 Aug
Externally publishedYes

Keywords

  • alpha1A/D-adrenoceptor
  • bladder
  • naftopidil
  • phosphodiesterase type 5 inhibitor
  • rat
  • spinal cord injury
  • tadalafil
  • urethra

ASJC Scopus subject areas

  • Clinical Neurology
  • Urology

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