title: The effect of nitric oxide inhibition on ischemic brain edema.
abstract: The involvement of nitric oxide (NO) in the development of ischemic cytotoxic edema was investigated by inhibiting nitric oxide synthase (NOS) activity with N omega-nitro-L-arginine (NLA). Bilateral carotid artery occlusion (15 min) alone or with release (15 and 60 min) served as a model for edema induction. NLA, N omega-nitro-D-arginine methyl ester (D-NAME) or Ringer's solution were administered 4 hr prior to ischemia or sham operation. Treatment with a stable nitroxide radical, 4-hydroxy-2,2, 6,6-tetramethylpiperidine-L-oxyl (TPL), was used to assess free radical involvement in edema. Accumulation of tissue water was evaluated by measuring specific gravity (SG) of brain cortex and histological examination. There was a greater reduction of cortical SG in early reperfusion (15 min) and a lesser decrease in SG (60 min later) in NLA-than in D-NAME- or Ringer's-treated gerbils. The NLA effect was confirmed by histological examination of the brain tissue. TPL treatment (pre- and postischemic) ameliorated the formation of edema to the same degree as NLA. The findings indicate a biphasic NLA modulation of cytotoxic edema most likely mediated through absence or presence of NO-derived free radicals.
authors.affiliation: Stroke Branch, NINDS, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yasuma
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.forename: C
authors.initials: C
authors.lastname: Ruetzel
authors.forename: R M
authors.initials: RM
authors.lastname: McCarron
authors.forename: M
authors.initials: M
authors.lastname: Spatz
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy*; D002545:Brain Ischemia / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005849:Gerbillinae; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester