title: Roles of neuronal nitric oxide synthase, oxidative stress, and propofol in N-methyl-D-aspartate-induced dilatation of cerebral arterioles.
abstract: BACKGROUND
  It remains unclear whether N-methyl-D-aspartate (NMDA) receptors contribute to cerebral parenchymal vasodilatation, and any effects of clinically used anaesthetics on the dilatation. The present study was designed to examine whether NMDA induces neuronal nitric oxide synthase (NOS)-mediated dilatation, in the cerebral parenchymal arterioles, and whether propofol and superoxide modulate the dilatation in relation to the NMDA receptor activation.
  
  
  METHODS
  The cerebral parenchymal arterioles within rat brain slices were monitored by a computer-assisted microscopy, and the vasodilatation in response to NMDA (10(-7) to 10(-5) M) was evaluated. Immunofluorescence analysis to neuronal and endothelial NOS and measurement of levels of superoxide and nitric oxide within the arteriole were simultaneously performed.
  
  
  RESULTS
  Propofol, an NMDA receptor antagonist MK801, and a neuronal NOS antagonist S-methyl-l-thiocitrulline (SMTC) reduced NMDA-induced dilation, whereas a superoxide inhibitor, Tiron, and NADPH oxidase inhibitor, gp91ds-tat, augmented NMDA-induced dilatation. Immunofluorescence analysis revealed distribution of neuronal NOS in both endothelial and smooth muscle cells in addition to neuronal cells. NMDA-induced superoxide and nitric oxide within the parenchymal arterioles. The increased superoxide within the arteriole was similarly inhibited by MK801, SMTC, gp91ds-tat, propofol, and a neuronal NOS antagonist vinyl-l-NIO, whereas the level of nitric oxide was reduced by MK801, SMTC, propofol, and vinyl-l-NIO, and it was augmented by gp91ds-tat.
  
  
  CONCLUSIONS
  NMDA dilates cerebral parenchymal arterioles possibly via neuronal NOS activation, whereas it produces superoxide via NADPH oxidase. In these arterioles, propofol reduces both the dilatation and superoxide production in response to NMDA.
authors.affiliation: Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hama-Tomioka
authors.forename: H
authors.initials: H
authors.lastname: Kinoshita
authors.forename: K
authors.initials: K
authors.lastname: Nakahata
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Azma
authors.forename: S
authors.initials: S
authors.lastname: Kawahito
authors.forename: N
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: N
authors.initials: N
authors.lastname: Matsuda
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D018715:Microscopy, Video; D016202:N-Methylaspartate / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018686:Anesthetics, Intravenous; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D013481:Superoxides; D009569:Nitric Oxide; D016202:N-Methylaspartate; D015237:Dinoprost; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; D015742:Propofol