Nitric oxide synthase inhibition by L-NAME prevents brain acidosis during focal cerebral ischemia in rabbits

Luca Regli, Mark C. Held, Robert E. Anderson, Fredric B. Meyer

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

This experiment examined the effects of nitric oxide (NO) synthase inhibition on brain intracellular pH, regional cortical blood flow, and NADH fluorescence before and during 3 h of focal cerebral ischemia using in vivo fluorescence imaging. Thirty fasted rabbits under 1% halothane were divided into four treatment groups receiving NO(ω)-nitro-L-arginine methyl ester (L- NAME) intravenously at 20 min prior to ischemia (0.1, 1, and 10 mg/kg and 1 mg/kg + 5 mg/kg L-arginine) and two control groups (nonischemic and ischemic). In ischemic controls, brain pH(i) declined to 6.73 ± 0.03 at 30 min and remained acidotic through the remainder of the ischemic period. In the 0.1 mg/kg group, brain pH(i) fell after 30 min of ischemia to 6.76 ± 0.05 (p < 0.05), but then improved progressively despite occlusion. In the 1 mg/kg group, brain pH(i) remained normal despite middle cerebral artery (MCA) occlusion. In the 10 mg/kg group and in the combined L-NAME + L-arginine group, pH(i) fell after 30 min of ischemia to 6.81 ± 0.03 (p < 0.05) and remained acidotic. During occlusion, regional cortical blood flow dropped in a dose-dependent manner. After 3 h of ischemia, regional cortical blood flow was 33.9 ± 10.9 and 25.1 ± 8.9 ml/100 g/min at doses of 0.1 and 10.0 mg/kg, respectively. L-NAME treatment did not significantly alter the increased NADH fluorescence that accompanied occlusion. This study shows that L-NAME can prevent intracellular brain acidosis during focal cerebral ischemia independent from regional cortical blood flow changes. This experiment suggests that NO is involved in pH(i) regulation during focal cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)988-995
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume16
Issue number5
DOIs
StatePublished - Jan 1 1996

Keywords

  • Focal cerebral ischemia
  • Intracellular pH
  • N(ω)- nitro-L-arginine methyl ester (L-NAME)
  • NAD/NADH
  • Nitric oxide

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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