1128 SILDENAFIL INDUCES THE EXPRESSION OF NEUROTROPHIC FACTORS AND DOWN REGULATION OF INFLAMMATORY CYTOKINES IN THE PELVIC GANGLIA NEURONS AFTER BILATERAL CAVERNOSAL NERVE RESECTION

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111128 SILDENAFIL INDUCES THE EXPRESSION OF NEUROTROPHIC FACTORS AND DOWN REGULATION OF INFLAMMATORY CYTOKINES IN THE PELVIC GANGLIA NEURONS AFTER BILATERAL CAVERNOSAL NERVE RESECTION Su Hlaing, Leah A. Garcia, Istvan Kovanecz, Jorge N. Artaza, and Monica G. Ferrini Su HlaingSu Hlaing Los Angeles, CA More articles by this author , Leah A. GarciaLeah A. Garcia Los Angeles, CA More articles by this author , Istvan KovaneczIstvan Kovanecz Torrance, CA More articles by this author , Jorge N. ArtazaJorge N. Artaza Los Angeles, CA More articles by this author , and Monica G. FerriniMonica G. Ferrini Los Angeles, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.725AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction is one of the complications associated with radical prostatectomy (RP) due to damage of the cavernosal nerves. The treatment with phosphodiesterase 5 (PDE5) inhibitors such as sildenafil preserves penile corporal smooth muscle and ameliorates fibrotic degeneration normally seen after bilateral cavernosal nerve resection (BCNR) in rats. However, the effect of PDE5 inhibitors on the pelvic ganglia neurons affected by BCNR is unknown. We aim to determine the gene expression profile of pelvic ganglia neurons after BCNR and subsequent treatment with sildenafil in relation to neurotrophic related-pathways. METHODS 5 month old Fisher rats were subjected to BCNR or sham operation and treated with or without sildenafil (20 mg/Kg. B.W. drinking water) for 7 days. Total RNA isolated from pelvic ganglia was subjected to reverse transcription and then to RT-PCR with the RAT- neurotrophic array. We only considered significant those genes that demonstrated a ± 2.0 fold change from its respective controls. In order to demonstrate the effects of sildenafil and BCNR on the pelvic ganglia neurons that innervate the penis, another set of animals were injected with 4% Fluorogold in the base of the penis 7 days before BCNR or Sham operation and were sacrificed 7 days post surgery. Sections of pelvic ganglia were used for immunohistochemistry (IMM) with antibodies against neurturin, nNOS, TH and heme oxygenase 1 (HO-1). RESULTS Comparison of the array data from sham versus BCNR at 7 days revealed a decreased expression of neurotrophic genes such as, Brain derived neurotrophic factor (BDNF=−2.00), neuroregulin 1 and 2 (NRG1=−2.00; NRG2=−8.00), neurturin (Nrtn=−2.00), neuronal nitric oxide synthase (nNOS=−2.00) and vascular growth factor (VGF=−2.43) and up-regulation of inflammatory cytokines such as Interleukin 1 beta (IL1b=2.55), interleukin 6 (Il6=3.36) .The treatment with Sildenafil after BCNR reversed the process by inducing an up-regulation of genes such as, BDNF=4.23, nNOS= 2.11; Nrtn=2.80 and NRG1=2.27 and a down regulation of the inflammatory cytokines. The results were confirmed by IMM on fluorogold labeled neurons for the expression of Nrtn, nNOS and HO-1. CONCLUSIONS Sildenafil promotes a down regulation of genes involved in neuropathic pain and changes in the neurotrophic factors leading to a regenerative state of the pelvic ganglia neurons. This study provides a justification for the use of PDE5 inhibitors as a neuro protective agent after BCNR. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e453 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Su Hlaing Los Angeles, CA More articles by this author Leah A. Garcia Los Angeles, CA More articles by this author Istvan Kovanecz Torrance, CA More articles by this author Jorge N. Artaza Los Angeles, CA More articles by this author Monica G. Ferrini Los Angeles, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...