title: Putative role of nitric oxide synthase isoforms in the changes of nitric oxide concentration in rat brain cortex and cerebellum following sevoflurane and isoflurane anaesthesia.
abstract: We have previously observed an increase in nitric oxide (NO) content in rat brain cortex following halothane, sevoflurane or isoflurane anaesthesia. This study was undertaken in order to determine whether isoform-specific nitric oxide synthase (NOS) inhibitors and inducers could modify these increases in NO contents. Rats were subjected to isoflurane and sevoflurane anaesthesia with concomitant administration of neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitro-indazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) or lipopolysaccharide. NO concentration in different organs was measured by electron paramagnetic resonance (EPR) spectroscopy. 7-NI significantly decreased NO concentration in cerebellum but not in brain cortex, whereas AMT decreased NO in all the organs studied. Anaesthesia significantly increased NO concentration in brain cortex and decreased that in cerebellum. AMT abolished the NO increase in brain cortex. Anaesthesia enhanced the drastic increase in NO concentration in brain cortex after intraventricular lipopolysaccharide administration. Isoflurane was found to inhibit recombinant nNOS and iNOS activities at high concentrations (EC50=20 mM). Our data suggest a putative role for iNOS in the increase in NO levels produced by isoflurane and sevoflurane, whereas nNOS activity is probably inhibited during anaesthesia.
authors.affiliation: Latvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga, LV-1006, Latvia. Nikolajs.Sjakste@lu.lv
authors.forename: Nikolajs
authors.initials: N
authors.lastname: Sjakste
authors.forename: Jelizaveta
authors.initials: J
authors.lastname: Sjakste
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boucher
authors.forename: Larisa
authors.initials: L
authors.lastname: Baumane
authors.forename: Tatjana
authors.initials: T
authors.lastname: Sjakste
authors.forename: Maija
authors.initials: M
authors.lastname: Dzintare
authors.forename: Dainuvite
authors.initials: D
authors.lastname: Meirena
authors.forename: Jelena
authors.initials: J
authors.lastname: Sharipova
authors.forename: Ivars
authors.initials: I
authors.lastname: Kalvinsh
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D007527:Isoenzymes; D008738:Methyl Ethers; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D009569:Nitric Oxide; D000077149:Sevoflurane; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat