title: Inhibition of neuronal nitric oxide synthase reduces isoflurane MAC and motor activity even in nNOS knockout mice.
abstract: BACKGROUND
  The glutamate-nitric oxide-cyclic GMP pathway has been identified as a potential target for volatile anaesthetic agents as acute inhibition of nitric oxide synthase (NOS) reduces the minimum alveolar concentration (MAC) in most animal studies. However, mice deficient in the type I NOS isoform (nNOS) are reported to have a similar MAC for isoflurane and are not affected by non-isoform specific inhibitors.
  
  
  METHODS
  We determined whether the nNOS specific inhibitor, 7-nitroindazole (7-NI), had an effect on isoflurane MAC and righting reflex (RRF) and investigated spontaneous motor activity in an open-field study in wild-type (WT) and knockout (KO) mice.
  
  
  RESULTS
  7-NI reduced isoflurane MAC and RRF in both WT and KO animals (all P<0.04). 7-NI profoundly reduced spontaneous motor activity in both the WT and KO animals in the open-field study as indicated by a reduction in the number of line crossings and rearings in both WT and KO mice (both P<0.001).
  
  
  CONCLUSIONS
  We conclude that isoform specific inhibition of nNOS reduces MAC and spontaneous motor activity even in nNOS KO animals. Our results indicate that the NMDA receptor-nitric oxide-cyclic GMP pathway remains a credible target in modulating the effects of isoflurane.
authors.affiliation: Academic Unit of Anaesthesia and Intensive Care, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK. t.engelhardt@abdn.uk
authors.forename: T
authors.initials: T
authors.lastname: Engelhardt
authors.forename: P R
authors.initials: PR
authors.lastname: Lowe
authors.forename: H F
authors.initials: HF
authors.lastname: Galley
authors.forename: N R
authors.initials: NR
authors.lastname: Webster
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007191:Indazoles; D001120:Arginine; D007530:Isoflurane; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole