title: Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress.
abstract: BACKGROUND
  Vascular dysfunction induced by hyperglycemia has not been studied in cerebral parenchymal circulation. The current study was designed to examine whether high glucose impairs dilation of cerebral parenchymal arterioles via nitric oxide synthase, and whether propofol recovers this vasodilation by reducing superoxide levels in the brain.
  
  
  METHODS
  Cerebral parenchymal arterioles in the rat brain slices were monitored using computer-assisted videomicroscopy. Vasodilation induced by acetylcholine (10 to 10 m) was obtained after the incubation of brain slices for 60 min with any addition of l-glucose (20 mm), d-glucose (20 mm), or propofol (3 x 10 or 10 m) in combination with d-glucose (20 mm). Superoxide production in the brain slice was determined by dihydroethidium (2 x 10 m) fluorescence.
  
  
  RESULTS
  Addition of d-glucose, but not l-glucose, reduced arteriolar dilation by acetylcholine, whereas the dilation was abolished by the neuronal nitric oxide synthase inhibitor S-methyl-l-thiocitrulline (10 m). Both propofol and the superoxide dismutase mimetic Tempol (10 m) restored the arteriolar dilation in response to acetylcholine in the brain slice treated with d-glucose. Addition of d-glucose increased superoxide production in the brain slice, whereas propofol, Tempol, and the nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase inhibitor apocynin (1 mm) similarly inhibited it.
  
  
  CONCLUSIONS
  Clinically relevant concentrations of propofol ameliorate neuronal nitric oxide synthase-dependent dilation impaired by high glucose in the cerebral parenchymal arterioles via the effect on superoxide levels. Propofol may be protective against cerebral microvascular malfunction resulting from oxidative stress by acute hyperglycemia.
authors.affiliation: Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakahata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Azma
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Matsuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Hama-Tomioka
authors.forename: Masanori
authors.initials: M
authors.lastname: Haba
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hatano
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D018715:Microscopy, Video; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013908:Thoracotomy; D014699:Venules / Q000187:drug effects / Q000502:physiology*
chemical_list: D005947:Glucose; D015742:Propofol