PD19-05 THERAPEUTIC EFFECTS OF PDE9 INHIBITOR IN STORAGE AND VOIDING DYSFUNCTION IN MICE WITH SPINAL CORD INJURY (SCI)

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2018PD19-05 THERAPEUTIC EFFECTS OF PDE9 INHIBITOR IN STORAGE AND VOIDING DYSFUNCTION IN MICE WITH SPINAL CORD INJURY (SCI) Nobutaka Shimizu, Ei-ichiro Takaoka, Takahisa Suzuki, Joonbeom Kwon, Mamoru Hashimoto, Hirotsugu Uemura, Akihide Hirayama, Anthony J Kanai, William C de Groat, and Naoki Yoshimura Nobutaka ShimizuNobutaka Shimizu More articles by this author , Ei-ichiro TakaokaEi-ichiro Takaoka More articles by this author , Takahisa SuzukiTakahisa Suzuki More articles by this author , Joonbeom KwonJoonbeom Kwon More articles by this author , Mamoru HashimotoMamoru Hashimoto More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Akihide HirayamaAkihide Hirayama More articles by this author , Anthony J KanaiAnthony J Kanai More articles by this author , William C de GroatWilliam C de Groat More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.995AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Phosphodiesterase (PDE) inhibitors, which can modulate cGMP or cAMP levels in tissues, such as PDE type 5 inhibitors have been used for the treatment of lower urinary tract dysfunction (LUTD). However, it remains to be elucidated whether PDE type 9 (PDE9) is involved in LUTD induced by SCI. Therefore, we investigated the effects of a PDE9 inhibitor (PDE9i) to clarify the role of PDE9 in storage and voiding dysfunction using SCI mice. METHODS C57BL/6N mice were used, and SCI was induced by complete transection of the Th8/9 spinal cord. Two weeks after SCI, PDE9i (5 mg/kg/day) or saline (treatment or control group, respectively) was administered daily by i.p. injection for 14days in. Four weeks after SCI, mice were evaluated using cystometry (CMG) under an awake condition. L6 dorsal root ganglia (DRG), urethral, bladder muscle and mucosal specimens were obtained from PDE9i and saline-treated SCI mice as well as saline-treated normal (spinal intact) mice to evaluate the levels of PDE9, TRPV1 and TNFα transcripts by real-time PCR RESULTS Compared to saline-treated SCI mice, non-voiding contractions during bladder filling were significantly reduced (Figure 1), and voiding efficiency was significantly improved in PDE9i-treated SCI mice (Figure 2). The levels of TRPV1 mRNA in DRG and bladder muscle were increased in SCI mice compared to spinal intact mice, and significantly decreased after PDE9i treatment in SCI mice. The TNFα mRNA levels in urethra, bladder muscle and mucosa were increased in SCI mice compared to spinal intact mice, and significantly decreased after PDE9i treatment in SCI mice. PDE9 transcripts were identified in L6 DRG and bladder tissues. CONCLUSIONS PDE9 inhibition improved SCI-induced detrusor overactivity and inefficient voiding, along with significant reductions in C-fiber afferent receptors such as TRPV1 and proinflammatory cytokines such as TNFα in mice. Thus, PDE9 could be a therapeutic target for storage and voiding LUTD after SCI. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e396-e397 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Nobutaka Shimizu More articles by this author Ei-ichiro Takaoka More articles by this author Takahisa Suzuki More articles by this author Joonbeom Kwon More articles by this author Mamoru Hashimoto More articles by this author Hirotsugu Uemura More articles by this author Akihide Hirayama More articles by this author Anthony J Kanai More articles by this author William C de Groat More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...