TY - JOUR
T1 - Nitric oxide synthase inhibition by L-NAME prevents brain acidosis during focal cerebral ischemia in rabbits
AU - Regli, Luca
AU - Held, Mark C.
AU - Anderson, Robert E.
AU - Meyer, Fredric B.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - Focal cerebral ischemia
KW - Intracellular pH
KW - N(ω)- nitro-L-arginine methyl ester (L-NAME)
KW - NAD/NADH
KW - Nitric oxide
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U2 - 10.1097/00004647-199609000-00024
DO - 10.1097/00004647-199609000-00024
M3 - Article
C2 - 8784244
AN - SCOPUS:0029780523
SN - 0271-678X
VL - 16
SP - 988
EP - 995
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 5
ER -