title: Endotoxin augments cerebral hyperemic response to halothane by inducing nitric oxide synthase and cyclooxygenase.
abstract: We examined the cerebral hyperemic response to halothane after treatment with bacterial lipopolysaccharide (LPS). To determine the involvement of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), we tested whether the effect of LPS on halothane-induced hyperemia was altered by pretreatment with the selective iNOS inhibitor, aminoguanidine (100 mg/kg), COX-2 inhibitor, NS-398 (5 mg/kg), or enzyme expression inhibitor, dexamethasone (4 mg/kg). Further, we examined whether the administration of a nitric oxide donor, diethylamine NONOate, would change the cerebral hyperemic response of halothane. Sprague-Dawley rats were anesthetized with 0.5 minimum alveolar anesthetic concentration of halothane and artificially ventilated. Regional cerebrocortical blood flow (rCBF) was assessed by laser-Doppler flowmetry. LPS (1 mg/kg) was administered intracerebroventricularly; artificial cerebrospinal fluid was used in controls. Four hours after LPS infusion, iNOS and COX-2 messenger ribonucleic acid (mRNA) levels (reverse transcription-polymerase chain reaction) and enzyme activities (arginine-citrulline conversion and prostaglandin E(2) enzyme immunoassay) were significantly increased. LPS enhanced halothane-induced 3.9 and 1.6-fold increases in rCBF at 1.0 and 1.5 minimum alveolar concentration, respectively. Co-treatment with NS-398 attenuated, but aminoguanidine or dexamethasone abolished the effect of LPS on halothane-induced rCBF increase. Diethylamine NONOate mimicked the enhanced rCBF response to halothane. These results suggest that LPS augmented halothane-induced cerebrocortical hyperemia by induction of iNOS and COX-2.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: R J
authors.initials: RJ
authors.lastname: Roman
authors.forename: J P
authors.initials: JP
authors.lastname: Kampine
authors.forename: A G
authors.initials: AG
authors.lastname: Hudetz
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000032:analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002956:Citrulline / Q000032:analysis; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology; D006940:Hyperemia / Q000139:chemically induced* / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017078:Laser-Doppler Flowmetry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009578:Nitrobenzenes / Q000494:pharmacology; D009589:Nitrogen Oxides; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D006834:Hydrazines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009578:Nitrobenzenes; D009589:Nitrogen Oxides; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D002956:Citrulline; D003907:Dexamethasone; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D001120:Arginine; D010544:Peroxidases; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C004479:pimagedine; D006221:Halothane