1005 VARDENAFIL DECREASES BLADDER AFFERENT NERVE FIRING IN UNANESTHETIZED DECEREBRATE SPINAL CORD-INJURED RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction1 Apr 20101005 VARDENAFIL DECREASES BLADDER AFFERENT NERVE FIRING IN UNANESTHETIZED DECEREBRATE SPINAL CORD-INJURED RATS Delphine Behr-Roussel, Stéphanie Oger, Stéphanie Caisey, Peter Sandner, Jacques Bernabé, and François Giuliano Delphine Behr-RousselDelphine Behr-Roussel Orsay, France More articles by this author , Stéphanie OgerStéphanie Oger Orsay, France More articles by this author , Stéphanie CaiseyStéphanie Caisey Orsay, France More articles by this author , Peter SandnerPeter Sandner Wüppertal, Germany More articles by this author , Jacques BernabéJacques Bernabé Orsay, France More articles by this author , and François GiulianoFrançois Giuliano Garches, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PDE5 inhibitors improve IPSS scores in BPH patients, despite a lack of effect on Qmax. Moreover, a single dose of vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by non-voiding contractions (NVC) during bladder filling due to functional and morphological plasticity of bladder afferent pathways resulting in an increased bladder afferent nerve firing (BANF). We postulated that vardenafil could improve urodynamic parameters by reducing BANF. We thus investigated concomitantly the effect of vardenafil on intravesical pressure (IVP) by cystometry experiments while recording single BANF in response to bladder filling. METHODS Complete T7-T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250-275 g). To avoid confounding effect of anesthesia, SCI rats were decerebrated at day 21-29 post-spinalization. Fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Afferent nerve fibers originating from the bladder were identified by electrical stimulation of the pelvic nerve and by bladder distension. First, bladder filling was performed to determine the maximal bladder filling volume (BFV). Then, bladders were stabilized at 75% of maximal BFV (non-noxious BFV). Saline (n=7) or vardenafil 1 mg/kg (n=8) was delivered iv. NVC were characterized by the force generated (AUC, in mmHg.s) while the frequency of BANF (spikes/s) was determined during 45 minutes. All results were expressed as % of baseline and compared using two-way ANOVA. RESULTS In all SCI rats, BANF was already present and regular at resting conditions (26.2±4.1spikes/s). During bladder filling, IVP slowly increased with transient NVC superimposed. Concomitantly, BANF progressively increased to reach a 2.4-fold increase at maximal BFV (2.65±0.28ml). After stabilization, the increase in BANF elicited by submaximal BFV was 186±37%. Vardenafil injection induced an immediate decrease in NVC compared to saline (p<0.001). Likewise, BANF also decreased very rapidly after vardenafil injection (52% decrease versus 28% in saline after 45 minutes, p<0.001). CONCLUSIONS Systemic administration of vardenafil strongly reduced both NVC and BANF elicited by submaximal bladder filling in unanesthetized decerebrate SCI rats. These findings may give us a new insight into the mechanism of action of PDE5 inhibitors at reducing storage symptoms i.e. in men with LUTS /BPH. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e391 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Delphine Behr-Roussel Orsay, France More articles by this author Stéphanie Oger Orsay, France More articles by this author Stéphanie Caisey Orsay, France More articles by this author Peter Sandner Wüppertal, Germany More articles by this author Jacques Bernabé Orsay, France More articles by this author François Giuliano Garches, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...