title: Dual effects of L-NAME during transient focal cerebral ischemia in spontaneously hypertensive rats.
abstract: The role of nitric oxide (NO) in ischemic neuronal injury is unclear. In permanent focal ischemia models, NO release has been reported to be both neuroprotective, by virtue of actions to improve cerebral blood flow (CBF) within ischemic tissue, and neurotoxic. Very little attention has been given to determining the role of NO in transient focal ischemia. In the present studies, low-dose NO inhibition using NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg/kg bolus, 0.01 mg.kg-1.min-1 iv) reduced infarct volume after 180 min of middle cerebral arterial occlusion (MCAO) and 120 min of reperfusion as measured via 2,3,5-triphenyltetrazolium chloride by 55% (P < 0.0001). Similar reductions occurred whether L-NAME was given throughout MCAO-reperfusion or just 30 or 60 min before reperfusion. L-NAME reduced CBF in the area of infarction at 30 and 180 min of MCAO by 36 and 33% (P < 0.02). In contrast, 15 min into reperfusion, L-NAME increased CBF in the area of infarction by 69% (P < 0.03) and by 27% in the contralateral homologous right hemisphere. Although vascular effects are present, these findings suggest a neurotoxic role for NO primarily during reperfusion after transient focal ischemic injury.
authors.affiliation: Department of Pediatrics, Loma Linda University School of Medicine, California 92350.
authors.forename: S
authors.initials: S
authors.lastname: Ashwal
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.forename: T N
authors.initials: TN
authors.lastname: Osborne
authors.forename: W J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002546:Ischemic Attack, Transient / Q000473:pathology* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester