In:
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 16, No. 6 ( 1996-11), p. 1143-1152
Abstract:
We investigated the role of nitric oxide (NO) in leukocyte-endothelium interaction, blood-brain barrier (BBB) function and oxygen free-radical production in the rat pial microcirculation. In a closed cranial window preparation (dura removed) over the parietal cortex of pentobarbital-anesthetized Wistar rats, NO synthase (NOS) was inhibited by systemic and/or topical application of N ω -nitro-l-arginine (l-NNA) under physiological conditions and during leukotriene B 4 (LTB 4 ) activation. Circulating leukocytes were labeled by intravenous injection of rhodamine 6G. We used a confocal laser scanning microscope (CLSM) and studied leukocyte rolling and sticking in pial veins and arteries before and after NOS inhibition. At the end of the experiments, sodium-fluorescein was injected intravenously to test BBB integrity. Brain cortex oxygen free-radical production was investigated in the cranial window preparation using lucigenin-enhanced chemiluminescence (CL). l-NNA application did not lead to significant changes in leukocyte-endothelium interaction, BBB function, and oxygen free-radical production under physiological conditions [leukocyte-endothelium interaction: control (n = 5), l-NNA systemically (n = 5), l-NNA topically (n = 5): at baseline rollers/100 μm: 0.76 ± 0.55, 0.64 ± 0.94, 0.44 ± 0.55 and stickers/100 μm: 0.90 ± 0.28, 0.76 ± 0.24, 0.84 ± 0.42; at 60 min rollers/100 μm: 1.49 ± 0.66, 1.21 ± 0.99, 0.67 ± 0.66 and stickers/100 μm: 1.04 ± 0.20, 1.19 ± 0.23, 1.21 ± 0.54; oxygen free-radical production (n = 4): CL count before l-NNA application 35 ± 17 cps, after 1 h of topical superfusion of l-NNA 38 ± 14 cps; p 〈 0.05]. In contrast to the results achieved under physiological conditions, a significant further increase of rolling leukocytes and BBB permeability occurred due to NOS inhibition under LTB 4 -activated conditions [76 ± 47% significant ( p ≤ 0.01, n = 7) further increase of rollers/100 μm due to 60 min l-NNA application following the activation period of 120 min LTB 4 superfusion]. Our results support a modulatory role for NO in leukocyte-endothelium interaction and BBB permeability in the pial microcirculation when this interaction is increased.
Type of Medium:
Online Resource
ISSN:
0271-678X
,
1559-7016
DOI:
10.1097/00004647-199611000-00008
Language:
English
Publisher:
SAGE Publications
Publication Date:
1996
detail.hit.zdb_id:
2039456-1
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