title: Effects of L-arginine, mirabegron, and oxybutynin on the primary bladder afferent nerve activities synchronized with reflexic, rhythmic bladder contractions in the rat.
abstract: OBJECTIVE
  We measured single-unit mechanosensitive afferent activities (SAAs) during reflexic, rhythmic bladder contractions (RBCs), and examined whether L-arginine, an NO substrate, and mirabegron, a β3-adrenoceptor agonist, and oxybutynin, an antimuscarinic agent, can affect the SAAs in such condition.
  
  
  METHODS
  Twenty-nine female Sprague-Dawley rats were anesthetized. SAA was identified by electro-stimulation of the left pelvic nerve and by bladder distension, and was divided into Aδ- or C-fibers by conduction velocity. To produce the RBCs, right L6 dorsal roots were kept intact. Under an isovolumetric condition, vehicle and L-arginine (300 mg/kg) or mirabegron (1 mg/kg) or oxybutynin (1 mg/kg) were administered intravenously.
  
  
  RESULTS
  All of the Aδ- (n = 26) and C-fibers (n = 29) capable of responding to bladder distention were also responsive to bladder contractions during RBCs. The amplitude and duration of RBCs significantly decreased after mirabegron- and oxybutynin-administrations, but not after L-arginine-administration. The interval of RBC was significantly elongated after L-arginine- and mirabegron-administrations. Regarding the SAAs, the peaks of firing rate (FR) during RBCs and FR during the non-contractile phase were decreased after L-arginine-administration, which were more remarkable for Aδ-fibers than C-fibers. Similar results were observed after mirabegron-administration only for Aδ-fibers. After oxybutynin-administration, the peak of FR of both fiber-SAAs significantly decreased, but the change was not significant when the value was normalized by the amplitude of RBCs.
  
  
  CONCLUSIONS
  The present results indicate that mechanosensitive Aδ- and C-fibers were also responsive to bladder contractions, and that NO production and β3-adrenoceptor stimulation can inhibit SAAs mainly of Aδ-fibers synchronized with RBCs.
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D008333:Mandelic Acids / Q000494:pharmacology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010507:Periodicity; D011312:Pressure; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D013844:Thiazoles; D009569:Nitric Oxide; D001120:Arginine; C005419:oxybutynin; C520025:mirabegron
keywords: Sprague-Dawley rats; afferent; nitric oxide; urinary bladder; β3-adrenoceptor