title: Inhibitors of nitric oxide synthesis antagonize nitrous oxide antinociception in mice and rats.
abstract: Administration of the anesthetic gas N2O evoked an antinociceptive effect in two rodent antinociception paradigms. In the mouse abdominal constriction test, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NG-nitroarginine (L-NOARG) caused dose-related antagonism of the antinociceptive effect of N2O but not of either morphine or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate. This antinociceptive effect was also antagonized by systemic pretreatment with the NOS inhibitors L-NG-nitroarginine methyl ester (L-NAME) and L-NG-monomethylnitroarginine. The antagonism of N2O by L-NOARG and L-NAME was completely reversed by i.c.v. administration of L-arginine but not D-arginine. In the absence of NOS inhibition, N2O antinociception was potentiated by i.c.v. treatment with L-arginine but not D-arginine. The i.c.v. pretreatment with L-NAME also reduced N2O antinociception; this antagonism was also stereospecifically reversed by L-arginine. In the rat hot plate test, the antinociceptive response to 70% N2O was antagonized in dose-related manner by i.c.v. pretreatment with L-NOARG or L-NAME. N2O antinociception was restored by i.c.v. treatment with L-arginine but not D-arginine. However, neither L-arginine nor D-arginine alone affected N2O antinociception. These results implicate a key role for NO in the mediation of the antinociceptive effects of N2O in both mice and rats.
authors.affiliation: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford.
authors.forename: C E
authors.initials: CE
authors.lastname: McDonald
authors.forename: M J
authors.initials: MJ
authors.lastname: Gagnon
authors.forename: E A
authors.initials: EA
authors.lastname: Ellenberger
authors.forename: B L
authors.initials: BL
authors.lastname: Hodges
authors.forename: J K
authors.initials: JK
authors.lastname: Ream
authors.forename: S A
authors.initials: SA
authors.lastname: Tousman
authors.forename: R M
authors.initials: RM
authors.lastname: Quock
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D001120:Arginine; D009609:Nitrous Oxide; D019331:NG-Nitroarginine Methyl Ester