title: Neuronal-derived nitric oxide modulates the activity of mouse detrusor smooth muscle.
abstract: OBJECTIVE
  We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle.
  
  
  METHODS
  Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS(-/-) ) mice and their wild type siblings (nNOS(+/+) ). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca(2+) imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS(+/+) mouse detrusor strips.
  
  
  RESULTS
  In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca(2+) flashes in nNOS(-/-) preparations was lower than that in the nNOS(+/+) preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100 µM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10 µM). 7-NI (100 µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips.
  
  
  CONCLUSIONS
  We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies.
authors.affiliation: Department of Surgery, National Defense Medical Center, Taipei, Taiwan, Republic of China. en.meng@gmail.com
authors.forename: E
authors.initials: E
authors.lastname: Meng
authors.forename: J S
authors.initials: JS
authors.lastname: Young
authors.forename: T L
authors.initials: TL
authors.lastname: Cha
authors.forename: G H
authors.initials: GH
authors.lastname: Sun
authors.forename: D S
authors.initials: DS
authors.lastname: Yu
authors.forename: A F
authors.initials: AF
authors.lastname: Brading
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*
chemical_list: D006834:Hydrazines; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D052248:Nitric Oxide Synthase Type I