title: The role of 20-hydroxyeicosatetraenoic acid in cerebral arteriolar constriction and the inhibitory effect of propofol.
abstract: BACKGROUND
  We conducted this study to examine, in cerebral parenchymal arterioles, whether 20-hydroxyeicosatetraenoic acid (20-HETE) induces constrictor responses via superoxide and whether propofol reduces this constriction.
  
  
  METHODS
  Electrical field stimulation or 20-HETE was applied to rat brain slices monitored by computer-assisted microscopy. In some experiments, a Na(+) channel antagonist tetrodotoxin, a 20-HETE synthesis inhibitor HET0016, a superoxide scavenger, Tiron, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium (DPI) and gp91ds-tat, or propofol was added. The superoxide level in the brain slice and the production rate in the absence of slices were evaluated by dihydroethidium fluorescence or cytochrome c reduction with a superoxide-generating system, respectively.
  
  
  RESULTS
  Electrical stimulation induced constriction of the cerebral parenchymal arteriole, whereas this response was abolished by tetrodotoxin, HET0016, Tiron, or DPI. 20-HETE (10(-8)-10(-6) mol/L) produced arteriolar constriction, which was inhibited by Tiron or DPI. Propofol reduced the constriction induced by electrical stimulation or 20-HETE. 20-HETE induced superoxide production in the brain slice, which was reduced by Tiron, gp91ds-tat, or propofol. However, propofol did not alter the superoxide production rate in the absence of brain slices.
  
  
  CONCLUSIONS
  Either neuronal transmission-dependent or exogenous 20-HETE seems to induce cerebral parenchymal arteriolar constriction via superoxide production resulting from NADPH oxidase activation. Propofol is likely to prevent this constriction via inhibition of NADPH oxidase, but not by its scavenging effect on superoxide.
authors.affiliation: Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hama-Tomioka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Azma
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakahata
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
authors.forename: Noboru
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D002474:Cell-Free System; D002536:Cerebral Arteries / Q000187:drug effects* / Q000201:enzymology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018715:Microscopy, Video; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000578:Amidines; D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006023:Glycoproteins; C000708209:HET0016; D006893:Hydroxyeicosatetraenoic Acids; D009861:Onium Compounds; D026941:Sodium Channel Blockers; C473031:gp91ds-tat protein, chimeric; D013481:Superoxides; D013779:Tetrodotoxin; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C007517:diphenyleneiodonium; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D019255:NADPH Oxidases; D015742:Propofol