Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits

Robert E. Anderson, Fredric B. Meyer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume40
Issue number2
StatePublished - Aug 1996

Fingerprint

NG-Nitroarginine Methyl Ester
Brain Ischemia
Nitric Oxide Synthase
Rabbits
Acidosis
Reperfusion
Regional Blood Flow
NAD
Brain
Oxidation-Reduction
Drug and Narcotic Control
Optical Imaging
Halothane
Arginine
Ischemia
Control Groups

Keywords

  • Intermittent focal cerebral ischemia
  • Intracellular pH
  • NAD/NADH

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits. / Anderson, Robert E.; Meyer, Fredric B.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 40, No. 2, 08.1996.

Research output: Contribution to journalArticle

@article{f3bfc32b948f4935875a43e40f882585,
title = "Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits",
abstract = "The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5{\%} halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21{\%} (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.",
keywords = "Intermittent focal cerebral ischemia, Intracellular pH, NAD/NADH",
author = "Anderson, {Robert E.} and Meyer, {Fredric B.}",
year = "1996",
month = "8",
language = "English (US)",
volume = "40",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits

AU - Anderson, Robert E.

AU - Meyer, Fredric B.

PY - 1996/8

Y1 - 1996/8

N2 - The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.

AB - The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.

KW - Intermittent focal cerebral ischemia

KW - Intracellular pH

KW - NAD/NADH

UR - http://www.scopus.com/inward/record.url?scp=33750703226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750703226&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750703226

VL - 40

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 2

ER -