PD19-06 NO-RELEASING NANOPARTICLES DECREASE DETRUSOR OVERACTIVITY IN DNOS-/- KNOCKOUT AND TRANSGENIC SICKLE CELL MICE (2018)

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology I1 Apr 2018PD19-06 NO-RELEASING NANOPARTICLES DECREASE DETRUSOR OVERACTIVITY IN DNOS-/- KNOCKOUT AND TRANSGENIC SICKLE CELL MICE Serkan Karakus, Biljana Musicki, William Akakpo, Joel M. Friedman, Kelvin Davies, and Arthur L. Burnett Serkan KarakusSerkan Karakus More articles by this author , Biljana MusickiBiljana Musicki More articles by this author , William AkakpoWilliam Akakpo More articles by this author , Joel M. FriedmanJoel M. Friedman More articles by this author , Kelvin DaviesKelvin Davies More articles by this author , and Arthur L. BurnettArthur L. Burnett More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.996AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nitric oxide (NO) signaling pathway plays an important role in lower urinary tract, principally in the penis. Additionally, NO may contribute to the regulation of urethral and bladder smooth muscle tone. Sickle cell (SC) mouse model exhibit overactive bladder symptoms, but the mechanisms are not understood. We hypothesize that NO dysregulation causes overactive bladder, while NO-releasing nanoparticles (NO-NP), a novel NO delivery system, decreases detrusor overactivity, using eNOS- and nNOS-deficient (dNOS-/-) knockout and SC mice. METHODS SC (n=18) and dNOS-/- knockout (n=22) mice were used as animal models of overactive bladder and compared to wild type (WT) (n=15) mice. Empty-NP or NO-NP were injected into the bladder. After 10 minutes, cystometric studies were performed. For molecular studies, bladder tissues were collected from separate groups of mice; the expression levels of proteins that regulate detrusor relaxation (nitric oxide synthase pathway) or contraction (RhoA/Rho-kinase pathway) were assessed. For statistical analysis, the Student's t-test and one-way analysis of variance (ANOVA) were used. RESULTS SC and dNOS-/- mice had significantly higher (P < 0.05) voiding and non-voiding contraction frequencies and significantly lower (P < 0.05) compliance compared to WT mice. NO-releasing nanoparticles normalized these abnormalities in both SC and dNOS-/- mice. RhoA/Rho-kinase pathway, reflected by phosphorylation of myosin phosphatase target subunit 1 (P-MYPT-1), was increased (P < 0.05) in the bladder of SC mice compared to WT, which was reversed by NO-releasing nanoparticles. eNOS phosphorylation on positive (Ser-1177) regulatory site was decreased (P < 0.05) in the bladder of SC mice compared to WT, which was reversed by NO-releasing nanoparticles. nNOS phosphorylation on Ser-1412 and VASP phosphorylation on Ser-239 (a substrate of protein kinase G-I and a marker of the integrity of the NO/cGMP signaling pathway) were not different between SC and WT mouse bladders. Empty-NP did not affect any of the measured parameters. CONCLUSIONS Dysregulation of NO and RhoA/Rho-kinase pathways is associated with detrusor overactivity in SC mice; NO-releasing nanoparticles reverse these molecular derangements in the bladder and decrease detrusor overactivity. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e397 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Serkan Karakus More articles by this author Biljana Musicki More articles by this author William Akakpo More articles by this author Joel M. Friedman More articles by this author Kelvin Davies More articles by this author Arthur L. Burnett More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...