24 EFFECTS OF MIRABEGRON, A β3-ADRENOCEPTOR AGONIST, ON THE PRIMARY BLADDER AFFERENT ACTIVITY SYNCHRONIZED WITH RHYTHMIC BLADDER CONTRACTIONS IN RATS IN COMPARISON WITH THOSE OF OXYBUTYNIN

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (1)1 Apr 201324 EFFECTS OF MIRABEGRON, A β3-ADRENOCEPTOR AGONIST, ON THE PRIMARY BLADDER AFFERENT ACTIVITY SYNCHRONIZED WITH RHYTHMIC BLADDER CONTRACTIONS IN RATS IN COMPARISON WITH THOSE OF OXYBUTYNIN Naoki Aizawa, Yukio Homma, and Yasuhiko Igawa Naoki AizawaNaoki Aizawa Tokyo, Japan More articles by this author , Yukio HommaYukio Homma Tokyo, Japan More articles by this author , and Yasuhiko IgawaYasuhiko Igawa Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1399AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES β3-adrenoceptor (β3-AR) agonists can inhibit the single unit mechanosensitve bladder afferent activities (SAAs) in response to bladder distension. These SAAs, however, might be enhanced also by bladder contractions. Therefore, we measured SAAs during rhythmic bladder contractions (RBCs) in an isovolumetric condition, and examined whether mirabegron, a β3-AR agonist, can affect the SAAs in such condition in rats, and compared with the effect of oxybutynin, an antimuscarinic agent. METHODS Twenty-five female SD rats were used. Under urethane anesthesia, SAAs were dissected from the left L6 dorsal roots and identified by electrical stimulation of the left pelvic nerve and by bladder distension. Nerves were classified as an Aδ- or C-fiber by conduction velocity (2.5 m/second). To produce the RBCs, right L6 dorsal roots were kept intact and the urethral meatus was clamped. When RBCs were reproducibly induced by intravesical saline-instillation, the instillation was stopped and the bladder was kept under an isovolumetric condition. Then, vehicle and 1 mg/kg of mirabegron or oxybutynin were administrated intravenously. RESULTS After mirabegron-treatment, the amplitude and duration of RBCs significantly decreased. Similar effects were observed also after oxybutynin-treatment. The interval of RBCs increased and the basal pressure decreased significantly only after mirabegron-treatment. Forty-one single afferent fibers (Aδ-fibers: n=19, C-fibers: n=22) were isolated. SAAs of both Aδ- and C-fibers were enhanced in a fashion synchronized with RBCs. After mirabegron-treatment, the peak of FR (firing rate) of SAAs synchronized with RBCs significantly decreased in Aδ-fibers, but not C-fibers (figure). After oxybutynin-treatment, the peak of FR of both fiber-SAAs significantly decreased, but the change was not significant when the value was normalized by the change in the amplitude of RBCs. CONCLUSIONS The present results indicate that the stimulation of β3-AR by mirabegron can inhibit mechanosensitive primary bladder afferent activities synchronized with RBCs, mainly of Aδ-fibers. However, these effects were not observed with oxybutynin. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e9-e10 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naoki Aizawa Tokyo, Japan More articles by this author Yukio Homma Tokyo, Japan More articles by this author Yasuhiko Igawa Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...