Is intracellular brain pH a dependent factor in NOS inhibition during focal cerebral ischemia?

Robert E. Anderson, Fredric B. Meyer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The interaction between nitric oxide (NO.) and focal cerebral ischemia is multifaceted. Experiments have shown that inhibition of nitric oxide synthase (NOS) either ameliorates or exacerbates focal cerebral ischemia. Recent in vitro experiments have shown that NOS activity is pH-dependent. Previous work from this laboratory has demonstrated that N(G)-nitro-L-arginine-methyl-ester (L-NAME) mitigated cerebral ischemia independent from regional cerebral blood flow (rCBF) changes during moderate focal cerebral ischemia. This study examined the effects of L-NAME inhibition on brain pH(i), rCBF, and NADH redox state during 3 h of severe focal cerebral ischemia. Fifteen fasted rabbits under 1.5% halothane were equally divided into three groups: ischemic controls and two drug groups receiving either 1.0 or 10 mg/kg L-NAME intravenously 30 min prior to ischemia. In the ischemic controls, brain pH(i) declined from 6.95±0.04 to 6.60±0.05, rCBF declined from 48±7 to 10±3 ml/100 g/min, and NADH fluorescence increased by 149±15% 3 h after onset of ischemia (p<0.01 for all three parameters). L-NAME at either dose did not significantly alter these values. Infarct volume was not significantly different between both the L-NAME treated groups and the ischemic control group. This data suggests that during severe focal cerebral ischemia, NO. mechanisms of injury have a less important punitive role. One possible explanation is that the severity of acidosis secondary to anaerobic metabolism during severe focal cerebral ischemia attenuates NOS activity. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)220-226
Number of pages7
JournalBrain Research
Volume856
Issue number1-2
DOIs
StatePublished - Feb 19 2000

Keywords

  • Acidosis
  • Brain pH(i)
  • Cortical blood flow
  • Infarction
  • Nitric oxide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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