title: Antidiuretic effect of antimuscarinic agents in rat model depends on C-fibre afferent nerves in the bladder.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Antichollnergic agents are anticipated to diminish storage symptoms, as well as nocturia. Nevertheless, the effect of this treatment on polyuria related to nocturia is not clear. By subgroup analysis of the data set from a phase III clinical trial of antimuscarinic agent for OAB patients in Japan, imidafenacin was found to improve nocturia with a reduction in nocturnal polyuria. This study adds the effects and underlying mechanism of antimuscarinic agents decreasing urine production through inhibition of C-fibre in the bladder of water-leaded rats.
  
  
  OBJECTIVE
  To evaluate the effects and underlying mechanisms of antimuscarinic agents used to decrease in urine production in water-loaded rats.
  
  
  METHODS
  Urine production was measured using a cystostomy catheter in female Sprague-Dawley rats every 2 h. The effect of the antimuscarinic agents atropine, tolterodine and imidafenacin on urine production was investigated under water-loaded conditions, which were induced by i.p. injection of 15 mL saline. Blood samples were collected to determine the levels of antidiuretic hormone (ADH), aldosterone (ALD), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) before, and 2 and 8 h after, antimuscarinic agent administration. To induce desensitization of C-fibre afferent nerves, resiniferatoxin (RTX)was injected s.c. or intravesically 2 days before experiments.
  
  
  RESULTS
  Urine production increased and reached its maximum 2 h after 15 mL saline injection. Imidafenacin and tolterodine decreased urine production in water-loaded rats, but ADH, ALD, ANP and BNP levels were not different between imidafenacin-treated and vehicle-treated rats. The inhibitory effect on urine production was not found in RTX-treated rats. Atropine did not reduce urine production.
  
  
  CONCLUSIONS
  These results suggest that antimuscarinic agents decrease urine volume through C-fibres in the bladder; thus, antimuscarinics with inhibitory effects on C-fibres could be beneficial for nocturia with nocturnal polyuria.
authors: Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. noon@u-fukui.ac.jp
authors: Nozomu
authors: N
authors: Watanabe
authors: Hironobu
authors: H
authors: Akino
authors: Tetsuyuki
authors: T
authors: Kurokawa
authors: Minekatu
authors: M
authors: Taga
authors: Ryusei
authors: R
authors: Yokokawa
authors: Kazuya
authors: K
authors: Tanase
authors: Keiko
authors: K
authors: Nagase
authors: Osamu
authors: O
authors: Yokoyama
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects*; D053158:Nocturia / Q000188:drug therapy* / Q000503:physiopathology; D011141:Polyuria / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*; D014563:Urodynamics / Q000187:drug effects*
chemical_list: D018727:Muscarinic Antagonists